Infusion treatment agents, catheters, filter devices, and occlusion devices, and use thereof

ABSTRACT

Embodiments include an infusion-occlusion system having a delivery catheter, a guide catheter adapted to receive the delivery catheter, and a guidewire with an occlusion device adapted to be received within the guide catheter. The guide catheter of the catheter kit may be provided with an occlusion device at the distal end of the guide catheter. The delivery catheter may have an accessory lumen, coaxial or co-linear lumen, a supporting mandrel, or an occlusion device at its distal end. Moreover, according to some embodiments, occlusion devices may be a single material or a composite balloon having an inner liner and an outer layer of different materials, a high compliance low pressure balloon, or a filter device that restricts particles from passing through but does not restrict fluid, such as blood. An inflation device with a large volume and low volume syringe can be used to inflate the balloon.

This application is a Divisional application of copending applicationSer. No. 10/800,323, which is a Continuation-in-Part of co-pendingapplication Ser. No. 60/467,402, filed May 1, 2003, entitled “MultipleOcclusion Device”; and is a Continuation-in-Part of co-pendingapplication Ser. No. 10/387,048, filed Mar. 12, 2003, entitled “MultipleOcclusion Device”; and claims the priority benefit thereof.

BACKGROUND

Local treatment with a substance such as a drug at a particular internalsite of a patient, as opposed to systemic treatment, has becomeincreasingly important.

Such local access is useful not only for substance delivery but forother treatments, such as myocardial revascularization, as well.Myocardial revascularization forms “holes” in ischemic ventriculartissue to increase blood flow to the treated area.

For example, to achieve local treatment of tissue, physicians can usecatheters and occlusion devices. Specifically, cardiovascular guidecatheters are generally percutaneous devices that the physician advancesthrough a vasculature of a patient to a treatment region and are uses toguide other catheters or devices to the region. Delivery cathetersgenerally deliver a treatment agent to a treatment region in a patient'svasculature and typically are inserted through another catheter (e.g., aguide catheter). Additionally, occlusion devices, such as balloons, mayconnect to a delivery catheter to occlude a treatment region in thevasculature. Guidewires are generally devices that guide through thevasculature to a treatment region and typically can be inserted throughanother catheter (e.g., an introducer).

SUMMARY

In various embodiments, there is disclosed an infusion-occlusion systemfor infusing a treatment agent to a treatment region of an artery orvein (including a blood vessel of the human heart) that includes adelivery catheter, a guide catheter adapted to receive the deliverycatheter, a pressure increasing device adapted to be connected to thedelivery catheter, a pressure-sensing device adapted to be connected tothe delivery catheter, an inflation device adapted to be connected tothe delivery catheter, and a guidewire with an occlusion device adaptedto be received within the guide catheter. In another embodiment, theguide catheter of the catheter kit is provided with an occlusion deviceat the distal end of the guide catheter. In another embodiment, thedelivery catheter of the catheter kit is provided with an occlusiondevice at the distal end of the delivery catheter.

Examples of occlusion devices include balloons of a material anddimension to have an outer diameter that inflated to selected diameterswhen the balloon is inflated with a selected inflation pressure orvolume of gas or fluid. The balloon may be inflated by an inflationdevice having a high volume, low pressure syringe for initiallyinflating the balloon to a controlled low pressure initial diameter andhaving a low volume syringe for further inflating the balloon with acontrolled volume increment(s) to produce controlled diameterincrease(s) up the an occlusion diameter. Moreover, an occlusion devicemay be a composite balloon having an inner liner and an outer layer ofdifferent materials, a high compliance low pressure balloon, or a filterdevice that restricts particles from passing through but does notrestrict fluid, such as blood. Also, according to some embodiments,occlusion devices may include various types of balloons, such as a highcompliance low pressure balloons having a thermoplastic blend copolymermaterial with a polyether block amide resin moiety or a polyetheramidemoiety. Likewise, according to some embodiments, occlusion devices mayinclude various types of high-compliance low-tension balloons, such as acomposite or multi-layer expanded PolyTetraFlouroEthylene (ePTFE)balloon having an inner liner.

For instance, according to some embodiments, a catheter, such as a guidecatheter, may include a coronary sinus access guide with a collectioncage or filter device, to filter unwanted particles or material fromblood. Also, a delivery catheter may be a catheter that has a supportmandrel extending therethrough or may have lumen or tubes in a coaxialor co-linear orientation with the longitudinal axis of the catheter.

In another embodiment, there is disclosed a method of providingtreatment in a vessel of a patient that includes placing a guidecatheter in the vessel of the patient, feeding a delivery catheterthrough the guide catheter, where the delivery catheter is provided withan occlusion device at its distal end, feeding at least one guidewirewith an occlusion device through the guide catheter or the deliverycatheter, deploying the occlusion device(s) of the guidewire(s),deploying the occlusion device at the delivery end of the deliverycatheter, administering a treatment agent through the delivery catheter,disengaging all the occlusion devices, and removing the guidewire(s),the delivery catheter, and the guide catheter from the vessel of thepatient. In another embodiment, the method further provides foraspirating the vessel of the patient before disengaging all of theocclusion devices. Also described is are methods including occluding ablood vessel, infusing treatment agent, such as progenitor cells (suchas progenitor cells derived from bone marrow), to treat a treatmentregion of the blood vessel for a first time period, then allowing bloodor treatment agent perfusion or flow to the treatment region for asecond period of time, and repeating infusing and perfusion as necessaryto accomplish sufficient treatment.

Specific examples of apparatus to allow for blood or treatment agentperfusion or flow to the treatment region include occlusion balloonsthat can be deflated and inflated to selected outer diameter, cathetershaving perfusion lumen that bypass and exit holes in the catheter oneither end of the occlusion device, and catheters having guidewire lumenwith exit holes through the catheter proximal to the occlusion deviceand an exit port at the distal end of the catheter. Additional features,embodiments, and benefits will be evident in view of the figures anddetailed description presented herein.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 schematically illustrates a cross-section of the heart showingblood flow throughout the heart.

FIG. 2 schematically illustrates a vertical cross-section of the heart.

FIG. 3A illustrates a catheter system having a guide catheter, deliverycatheter, guide wires, and multiple occlusion devices.

FIG. 3B shows a sectional side view of FIG. 3A through line C-C′ of FIG.3A.

FIG. 4 schematically illustrates the placement of the catheters of FIGS.3A and 3B in the coronary sinus.

FIG. 5 schematically illustrates a guide catheter.

FIG. 6 shows a sectional view of FIG. 5 through line C-C′ of FIG. 5.

FIG. 7 is a side view of a cannula and a filter device in a sheath.

FIG. 8 is a view of FIG. 7 from perspective “A”.

FIG. 9 is a side view of a distal end of a cannula including a filterdevice having a distal portion with a second diameter that isapproximately the inner diameter of a blood vessel at a treatmentregion.

FIG. 10 is a view of FIG. 9 from perspective “B”.

FIG. 11 is a side section view of a filter device with a distal portionhaving a first diameter and balloons coupled to the filter device or thecannula.

FIG. 12 is a side-section view of a filter device with a distal portionhaving a second diameter, wherein the filter device is attached toinflated balloons which are attached to a cannula.

FIG. 13 is a side section view of a filter device with a distal portionhaving a third diameter, where the filter device is attached to deflatedballoons which are attached to a cannula.

FIG. 14 is a side sectional view of a filter device having a distalportion attached to tendons which pivot at pivot point and extendthrough a cannula.

FIG. 15 is a side section view of a filter device with a distal portionhaving a second diameter, wherein the filter device is attached totendons which extend through a cannula.

FIG. 16 is a side section view of a filter device with a distal portionhaving a third diameter and tendons attached to the distal portion andextending through a cannula.

FIG. 17 is a front cross sectional view of the filter device of FIG. 9showing a proximal portion of the filter device axially attached to anexterior surface of a cannula and lumens extending through the cannula.

FIG. 18 is a front cross sectional view of a filter device having aproximal portion axially attached to an exterior surface of a cannula,wherein the filter device has a helical spring shape.

FIG. 19 is a flow diagram of a process for using a filter device torestrain and aspirate particles.

FIG. 20 illustrates a guide catheter with an occlusion device.

FIG. 21 illustrates a telescoping guide catheter system.

FIG. 22 illustrates a balloon catheter tip with a guidewire.

FIG. 23 illustrates a balloon catheter tip proximal end.

FIG. 24 shows a section view of FIG. 23 through Line D-D′.

FIG. 25 schematically illustrates a delivery catheter system.

FIG. 26 schematically illustrates a side elevational view of a deliverycatheter.

FIG. 27 schematically illustrates a side view of the distal portion ofthe delivery catheter of FIG. 26.

FIG. 28 schematically illustrates transverse cross-sections of thedelivery catheter of FIG. 26 taken along the line 9-9.

FIG. 29 schematically illustrates transverse cross-sections of thedelivery catheter of FIG. 26 taken along the line 9-9.

FIG. 30 schematically illustrates a catheter system.

FIG. 31 schematically illustrates a sectional view of a catheter with aself inflating balloon.

FIG. 32 schematically illustrates the placement of a catheter in thecoronary sinus.

FIG. 33 schematically illustrates the diaphragmatic surface of theheart.

FIG. 34 schematically illustrates the sternocostal surface of the heart.

FIG. 35 schematically illustrates a partial cross-sectional perspectiveview of a catheter within the coronary sinus.

FIG. 36 illustrates a tapered balloon catheter tip.

FIG. 37 illustrates a balloon catheter tip with a guidewire.

FIG. 38 illustrates a balloon catheter tip with a guidewire.

FIG. 39 schematically illustrates a catheter within a vein.

FIG. 40 illustrates a guidewire tip with an occlusion device.

FIG. 41 illustrates a guidewire with an occlusion device.

FIG. 42 illustrates the guidewire of FIG. 41 with the occlusion deviceopen.

FIG. 42B, is a front view of FIG. 42A from perspective “A”.

FIG. 42C, is a side of the occlusion device of FIG. 42A showing theocclusion device overlapping leaflets.

FIG. 43 illustrates a guidewire with an occlusion device.

FIG. 44 is a cross-sectional view of a cannula and a balloon.

FIG. 45 is a cross-section view of a cannula and a lined ePTFE balloon.

FIG. 46 is a flow diagram of a process for forming a lined ePTFEballoon.

FIG. 47 is an elevated cut-away view of layers of ePTFE windings.

FIG. 48 is a cross section view of a cannula and a balloon.

FIG. 49A is a cross sectional view of a cannula and a balloon inflatedto occlude a blood vessel.

FIG. 49B may be a cross sectional view of FIG. 49A from perspective “A”,according to an embodiment.

FIG. 50 is a cross sectional view of a cannula and a postinflateddeflated balloon.

FIG. 51 is a cross sectional view of FIG. 48 from perspective “A”.

FIG. 52 is a cross sectional view of FIG. 49A from perspective “A”.

FIG. 53 is a cross sectional view of FIG. 50 from perspective “A”.

FIG. 54 is a flow diagram of a process for using a balloon to occlude ablood vessel or vein.

FIG. 55 illustrates a balloon outside diameter growth rate.

FIG. 56 illustrates a graph of blood vessel pressure over time.

FIG. 57 illustrates a cross-sectional view of a centrifugal pump.

FIG. 58 schematically illustrates a pressure increasing device.

FIG. 59 schematically illustrates a pressure increasing device.

FIG. 60 schematically illustrates a pressure transferring device.

FIG. 61 schematically illustrates a pressure-maintaining or dampeningdevice.

FIG. 62 schematically illustrates a pressure-maintaining or dampeningdevice with inlet and outlet.

FIG. 63 is a flow diagram of a method of treating a patient, inaccordance with an embodiment.

FIG. 64A is a cross sectional view of a cannula and a balloon.

FIG. 64B is a cross-sectional view the apparatus of FIG. 64A fromperspective “A”.

FIG. 65A shows the balloon and cannula of FIG. 64A, with the ballooninflated to a second inflation volume.

FIG. 65B is a cross-sectional view the apparatus of FIG. 65A fromperspective “A”.

FIG. 66A shows the cannula and balloon of FIG. 65A, with the ballooninflated to a third inflation volume.

FIG. 66B is a cross-sectional view the apparatus of FIG. 66A fromperspective “A”.

FIG. 67A shows the cannula and balloon of FIG. 66A, with the ballooninflated to a selected fourth inflation volume.

FIG. 67B is a cross-sectional view the apparatus of FIG. 67A fromperspective “A”.

FIG. 68 is a graph showing the relationship between the outer diameterof a balloon and the volume of inflation contrast fluid injected intothe balloon.

FIG. 69A is a side perspective view of a cannula having a balloonattached to its distal end and an infusion lumen and accessory lumenrunning through the cannula.

FIG. 69B is a cross section view of the first section of FIG. 69A fromperspective “A”.

FIG. 69C is a cross sectional view of the second section of FIG. 69Afrom perspective “B”.

FIG. 69D is a cross sectional view of the balloon section of FIG. 69Afrom perspective “C”.

FIG. 69E is a cross sectional view of the third section of FIG. 69A fromperspective “D”.

FIG. 69F is a cross section view of the fourth section of FIG. 69A fromperspective “E”.

FIG. 70 is a cross sectional view of the balloon section of FIG. 69Afrom perspective “C”, with the balloon inflated to a second volume thatis less than that shown in FIG. 69D.

FIG. 71A is a cross-sectional view of a cannula and a balloon, where thecannula includes coaxially aligned lumens.

FIG. 71B is a cross-sectional view of the apparatus of FIG. 71A fromperspective “A”.

FIG. 72A is a cross-sectional view of a cannula and a balloon, where thecannula includes coaxially and co-linearly aligned lumens.

FIG. 72B is a cross-sectional view of the apparatus of FIG. 72A fromperspective “B”.

FIG. 73 is a cross-sectional view of a cannula and a balloon, where thecannula has coaxially and co-linearly aligned lumens.

FIG. 74 is a cross-sectional view of the apparatus of FIG. 71A fromperspective “C” before forming tack joints between the guidewire tubeand the infusion tube.

FIG. 74B is the structure of FIG. 74A after forming tack joints betweenthe guidewire tube and the infusion tube.

FIG. 75A is a cross sectional view of an apparatus to inflate a lowvolume balloon to occlude a blood vessel.

FIG. 75B is a cross-sectional view of the apparatus of FIG. 75A fromperspective “A”.

FIG. 76 shows the latch mechanisms of FIG. 75A in an unlatched position.

FIG. 77 shows the latch mechanisms of FIG. 76 relatched.

FIG. 78 shows FIG. 77 after the inflation volume adjustment knob hasbeen rotated or turned to retain fluid.

FIG. 79 shows FIG. 78 after the inflation volume adjustment knob hasbeen rotated or turned to inflate the balloon with a selected inflationvolume fluid.

FIG. 80 shows FIG. 79 after unlatching inner the plunger lock to deflatethe balloon.

FIG. 81 shows an alternate embodiment of an apparatus to perform thefunctions of FIG. 75A-80.

FIG. 82 is a flow diagram of a process for treating a treatment regionof a blood vessel with one or more treatment agents or progenitor cells.

FIG. 83 is a cross-sectional view of an occlusion balloon attached to acannula having holes through an exterior surface of the cannulaproximate to the balloon, where the holes extend to a lumen in thecannula having an exit distal to the balloon.

FIG. 84 is a cross-sectional view of FIG. 83 from perspective “A”.

FIG. 85 is a cross-sectional view of the apparatus shown in FIG. 83advanced to a treatment region of a blood vessel.

FIG. 86 is a cross-sectional view of a cannula having a balloon attachedto its distal end and a bypass lumen extending from a hole distal to theballoon to a hole proximal to the balloon.

FIG. 87 shows the apparatus of FIG. 86 where the infusion lumen extendsto a location distal to balloon 8810.

FIG. 88 is a cross-sectional view of a cannula having a balloon attachedto its distal end, and infusion lumen to provide treatment agent to alocation distal to the balloon, and a bypass lumen to allow forperfusion of liquid from the location distal to the balloon to thelocation proximal to the balloon.

FIG. 89 is a cross-sectional view of a cannula having two balloonsattached to its distal end, and infusion lumen exiting the cannulabetween the balloons, and a bypass lumen to allow perfusion between alocation proximal to both balloons and a location distal to bothballoons.

DETAILED DESCRIPTION

Referring first to FIG. 1, a cross-sectional view of a heart is shown toillustrate blood flow throughout the heart. Deoxygenated blood returningfrom the body comes into heart 100 from either superior vena cava 126 orinferior vena cava 116 and collects in right atrium 122. Right atrium122 contracts to pump the blood through tricuspid valve 118 where itflows into right ventricle 114. Right ventricle 114 contracts to sendthe blood through pulmonary valve 120 into pulmonary artery 124 where itgoes into the lungs (not shown). The oxygenated blood returning from thelungs flows through pulmonary veins 102 where it flows into left atrium101. Left atrium 101 contracts sending the blood through bicuspid ormitral valve 104 and into left ventricle 108. When left ventricle 108contracts, the blood is sent through aortic valve 106 and into aorta128. Left ventricle 108 and right ventricle 114 are separated byventricular septum 110.

Referring to FIG. 2, a more detailed vertical cross-section of heart 100is shown. Blood first collects in right atrium 122 from superior venacava 126 or other veins. Right atrium 122 also includes right auricle142. When right atrium 122 contracts, blood is sent through tricuspidvalve 118 and into right ventricle 114. Tricuspid valve 118 is made upof three cusps: posterior cusp 176, septal cusp 178, and anterior cusp180 (shown retracted). Right ventricle 114 has a number of muscles thatcontract to send blood out of right ventricle 114. Some of the musclesin right ventricle 114 include right anterior papillary muscle 174(shown cut), and right posterior papillary muscle 172. Other parts ofthe anatomy of right ventricle 114 includes conus arteriosis 156, supraventricular crest 152, and moderator band 160 and septal band 162 ofseptal marginal trabacula 164. The blood outflow to the pulmonary trunkis marked by arrow 154. Pulmonary trunk is shown as 138. The bloodreturning from the lungs returns by left pulmonary veins 134 and rightpulmonary veins 136 where it collects in left atrium 101. Left atrium101 also includes left auricle 138. When left atrium 101 contracts,blood is sent through mitral valve 104 which is made up of posteriorcusp 132 and anterior cusp 130. Blood flows through mitral valve 104 andinto left ventricle 108. Muscles in the left ventricle include leftposterior papillary muscle 170, left anterior papillary muscle 168.Septum 110 separates left ventricle 108 from right ventricle 114. Septum110 includes the muscular part of intraventricular septum 186,interventricular part of the membranous septum 182, and the atrialventricular part of membranous septum 184. When left ventricle 108contracts, blood is sent through aortic valve 106 which includes leftsemi-lunar cusp 146, posterior semi-lunar (non-coronary) cusp 148, andright semi-lunar cusp 150. Most of the blood flows through aortic valve106 and into ascending aorta 128, although some of the blood is divertedinto the openings of coronary arteries 140.

Referring now to FIG. 3A, a catheter system having a guide catheter, adelivery catheter, guidewires and multiple occlusion system isillustrated. In various embodiments, system 300 includes guide catheter302 having proximal portion 305 and distal portion 306. System 300includes guide catheter 302 having lumen 304, for allowing system 300 tobe fed and maneuvered over a guidewire, such as guidewire 320 orguidewire 330. In various embodiments, lumen 304 extends the length ofguide catheter 302 from proximal portion 305 to distal portion 306.Representatively, in a procedure, a guidewire 320 or 330 may beinitially placed through a treatment region in a physiological lumen(e.g., a blood vessel) After placement, guide catheter 302 is advancedon and over the guidewire to or through a treatment region in an overthe wire (OTW) fashion. In another embodiment, system 300 may be a rapidtransfer type catheter assembly and only a portion of system 300 (e.g.,a distal portion) is advanced over the guidewire (also see FIG. 37).Guidewire 320 or guidewire 330 may be retracted or removed once system300 is placed at a treatment region.

System 300 includes guide catheter 302 having a lumen 304. Guidecatheter 302 includes distal portion 306 having occlusion balloon 308about distal portion 306. Delivery catheter 310 is shown disposedthrough lumen 304 of guide catheter 302. Delivery catheter 310 hasdistal end 312. Balloon 314 attaches at distal end 312. Notch 316 islocated at distal end 312 and guidewire opening 318 opens into lumen 313of delivery catheter 310 and is provided distally adjacent notch 316.Guidewire 320 is disposed through notch 316 and lumen 313 withindelivery catheter 310 and out guidewire opening 318 of delivery catheter310. Guidewire 320 includes distal end 322 and occlusion device 324.Occlusion device 324 may be an occlusion balloon attached to theexterior surface of guidewire 320 at or adjacent distal end 322 byadhesive, heat bonding, laser bonding, or shrink wrap bonding. Alsoshown disposed through guide catheter lumen 304 is guidewire 330.Guidewire 330 includes distal end 332 and occlusion device 334. Alsonote that occlusion device 334 may be an occlusion balloon attached tothe exterior surface of guidewire 330 at or adjacent distal end 332 byadhesive, heat bonding, laser bonding, or shrink-wrap bonding. In thisembodiment, guidewire 330 is shown disposed through guide catheter 302(e.g., from a proximal end to a distal end of the guide catheter) but isnot engaged by delivery catheter 310.

Proximal portion 305 of system 300 may reside outside the body of apatient while the remainder of system 300 is percutaneously introducedinto patient's vasculature through a blood vessel. As shown in FIG. 3A,proximal portion 305 of system 300 includes hub 351. Hub 351 includesguidewire 320, guidewire 330, and treatment agent delivery lumen 319. Invarious embodiments, relative to the materials for the various cannulasdescribed herein, a housing of hub 351 is a hard or rigid polymermaterial, e.g., a polycarbonate or acrylonitrile bubadiene styrene(ABS). A distal end of hub 351 has an opening to accommodate a proximalend of guide catheter 302. Hub 351 also has guidewire track 391,guidewire track 392, and a number of cavities at least partially throughhub 351 (extending in a distal to proximal direction) to accommodateguidewire 320, guidewire 330, and treatment agent delivery lumen 319.Treatment agent delivery lumen 319 may be used to infuse a treatmentagent including liquids, drugs, infusion pellets, suspended cells, stemcells, microspheres, peptides, growth factors, or various otherappropriate liquids, materials, and therapeutic agents (mixed with bloodor not) to be delivered locally or to a treatment region in a bloodvessel. Also, delivering a treatment agent may include performing aninfusate-uptake-enhancing procedure such as of electroporation,ultrasonic excitation, or photodynamic therapy. A proximal portion ofhub 351 flares to create a spacing between guidewire 320 and guidewire330, and treatment agent delivery lumen 319 (i.e., a distal end of hub351 has width W1 sufficient to accommodate a proximal end of guidecatheter 302 and a proximal end of hub 351 has width W2 that is greaterthan width W1). Hub 351 also includes medial section 390 which may havevarious appropriate lengths such as between a fraction of an inch and 10inches to allow hub 351 to function appropriately. Moreover, guidecatheter 302, delivery catheter 310, or hub 351 may include additionallumen, tubes, or cannula to inflate or expand occlusion devices,balloons, or to provide pressure measurements or pressure relief.

For example, in various embodiments, hub 351 may have at least thefollowing functions: guidewire movement and control, guide cathetermovement and control, delivery catheter movement and control, occlusiondevice expansion and retraction, balloon inflation and deflation,treatment agent delivery, and aspiration of fluid or particles from atreatment region of a blood vessel. With reference to FIG. 3A, in thisembodiment, hub 351 also includes strain relief 370 catheter holder 373(e.g., such as for holding a delivery catheter disposed through lumen304), treatment agent delivery port 323, guidewire port 398, andguidewire port 399. A proximal end of guide catheter 302 terminatesinside hub 351 near a distal end of hub 351. Guidewire 320, guidewire330, and treatment agent delivery lumen 319 extend proximally beyond aproximal end of guide catheter 302 and may be secured in respectivecavities through hub 351.

FIG. 3A also shows a distal portion of hub 351 including strained relief370. Strained relief 370 may be an elastic tubular component that mayact to reduce stress and inhibit shaft (e.g., of guide catheter 302)kinking for/or during the transition, movement, or control of aguidewire, such as guidewire 320 or guidewire 330, a catheter, such asguide catheter 302 or delivery catheter 320, or other functionsidentified above for hub 351.

FIG. 3B shows a sectional side view of FIG. 3A through line C-C′ of FIG.3A. FIG. 3B shows guidewire 320 and guidewire 330 disposed within lumen304 of guide catheter 302. FIG. 3B also shows delivery catheter 310disposed through guide catheter 302, wherein treatment agent deliverylumen 319 is disposed within delivery catheter 310.

According to various embodiments, the components of system 300, such asguide catheter 302, delivery catheter 310, balloon 308, balloon 314,occlusion devices 324 and 334, hub 351, strained relief 370, catheterholder 373, medial section 390, and other cannula or tubes surroundinglumens may be made of a material including materials described hereinfor such components, as well as materials described herein for balloons.For example, the components of system 300 may include a polycarbonate oracrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as apolyether block amide resin; a biocompatible polymer blend ofpolyurethane and silicone a polymer having a structure of a regularlinear chain of rigid polyamide segments interspaced with flexiblepolyether segments, a styrenic block copolymer (SBC), or a blend ofSBC's; a thermoplastic blend copolymer material having one of apolyether block amide resin moiety and a polyetheramide moiety; astyrene isoprene styrene (SIS), a styrene butadiene styrene (SBS), astyrene ethylene butylene styrene (SEBS), a polyetherurethane, an ethylpropylene, a ethylene vinyl acetate (EVA), an ethylene methacrylic acid,an ethylene methyl acrylate, and an ethylene methyl acrylate acrylicacid; a material from a material family of one of styrenic blockcopolymers and polyurethanes; a nylon material; a melt processiblepolymer; or a low durometer material. It is also contemplated that othercomponents of system, apparatus, or devices described herein, such asother catheters, cannulas, balloons, filter devices, occlusion devices,tubes (e.g., such as lumen 989, lumen surrounding material, lumensleeves, lumen cannula or lumen tubes, such as described below withrespect to infusion lumen 9520 or accessory lumen 9530 of FIGS. 69A-F),syringes, pressure increasing devices, pressure transfer devices,pressure maintaining devices, or pumps described below made of amaterial including materials described above.

In use, system 300 may be referred to as a “rapid transfer type system”designed to have the distal end of guide catheter 302 advancedpercutaneously to a desired first location in a blood vessel whereballoon 308 may be inflated to occlude the blood vessel or to fix thedistal end of guide catheter 302 at the first location. Note thatballoon 308 may be inflated later on in the use of system 300, such asafter delivery catheter 310 is advanced as described below. Next,guidewire 320 may be advanced percutaneously to a desired secondlocation in the same or a different blood vessel so that the distal end312 of delivery catheter 310 can be advanced or tracked over guidewire320 by feeding lumen 131 over guidewire 320. Then, balloon 314 may beinflated to occlude the blood vessel or to fix the distal end ofdelivery catheter 310 at or adjacent to the second location. It is alsocontemplated that guidewire 330 may be advanced through a blood vesseland to a third location. Occlusion devices 324 or 334 may be expanded toocclude blood vessels, such as at those locations, to define a distalend of a treatment region or treatment area. The treatment agent infusesinto the blood vessel from treatment agent delivery lumen 319 ofdelivery lumen 310 (e.g., where the region of interest, treatment agent,and infusion of treatment agent from the delivery catheter are inaccordance with corresponding descriptions herein).

For instance, in one example, guide catheter 302 may be fed andmaneuvered as described above into blood vessels of a person's heart.More particularly, FIG. 4 schematically illustrates the placement of thecatheters of FIGS. 3A and 3B in the coronary sinus, such as coronarysinus 3286 of FIGS. 32-33. As shown in FIG. 4, delivery catheter 310 maybe fed through lumen 304 of guide catheter 302 and into middle cardiacvein 406, such as by being fed through lumen 304 before or after guidecatheter 302 is placed through a treatment region in an OTW fashion, oris placed through a treatment region in a rapid transfer type fashion.Guidewire 320 may also be fed through guide catheter 302 throughguidewire opening 318 of delivery catheter 310 and into middle cardiacvein 406 distal to distal end 312 of delivery catheter 310. Guidewire330 may be fed through lumen 304 and into small cardiac vein 492. Next,occlusion device 324, occlusion device 334, and balloon 314 may beengaged to occlude small cardiac vein 492, and respectively occlude aportion of middle cardiac vein 406 between balloon 314 and occlusiondevice 334. Next, balloon 308 may be engaged. A treatment agent may befed through treatment agent delivery cannula 319 distal to balloon 314and proximal to occlusion device 324. Occlusion device 334 is engaged,and balloon 308 is engaged to prevent the treatment agent from reachingthe right atrium through shunts or anastimoses. Following the conclusionof the administration of the treatment agent, occlusion device 324,occlusion device 334, and balloon 314 may be disengaged, and guidewire320, delivery catheter 310, and guidewire 330 are removed from lumen 304of guide catheter 302. Then, coronary sinus 486 may be aspirated (e.g.,see hole 988 of FIG. 9 and accompanying text) and then balloon 308disengaged and guide catheter 302 removed from the coronary sinus.

Embodiments also include system 300 having a filter device instead ofballoon 308. For instance, the system and process described above forFIGS. 3A, 3B and 4 may also apply to a system and process having filterdevice 720, instead of and at the location of balloon 308, to restrainand aspirate particles shown and described below for FIGS. 7-19.

Referring now to FIG. 5, a guide catheter is illustrated. FIG. 5 showsguide catheter 502 which may or may not be or be part of system 300,such as if guide catheter 502 is part of guide catheter 302, as shownand described with respect to FIG. 3. In particular, guide catheter 502has proximal end 504 and distal end 506, which may be or be part ofproximal end 305 or distal end 306, as shown and described with respectto FIG. 3. Lumen 508 is shown in FIG. 5 extending through guide catheter502 from guide catheter opening 514 at proximal end 504 to distal end506. Guide catheter 502 also has balloon 510 attached around theexterior surface of catheter 502 at or adjacent distal end 506. Lumen508 or balloon 510 may correspond to lumen 304 or balloon 308, as shownand described with respect to FIG. 3. FIG. 5 also includes ballooninflation cannula 512 within guide catheter 502 from proximal end 504 toopening 513 within balloon 510.

FIG. 6 shows a sectional view of FIG. 5 through line C-C′ of FIG. 6. Asshown in FIG. 6, balloon inflation cannula 512 is disposed within guidecatheter 502 such as by being disposed through guide catheter opening514 and extended into a portion of balloon 510, such as to provideopening 513 to inflate balloon 510.

In various embodiments, proximal end 504 includes guide catheter opening514 and balloon inflation cannula 512. Also valve device 516, withselector mechanism 518. Guide catheter 502 may have an opening extendingfrom lumen 508 at distal end 506 to guide catheter opening 514 atproximal end 504. Thus, in embodiments implementing valve device 516,selector mechanism 518 may be disengaged to allow the opening extendingfrom lumen 508 to guide catheter opening 514 to remain open.Alternatively selector mechanism 518 may be engaged, such as by turning,to cause valve device 516 to close the opening between lumen 508 andguide catheter opening 514 at valve device 516 and instead direct anyfluid flowing through the opening and toward guide catheter opening 514through nozzle 520 and out of valve device 516. In some embodiments, thefluid flows such as into collecting reservoir 524, which in someembodiments connected to nozzle 520 such as by a hose connected tonozzle 520. Thus, selector mechanism 518 is engaged, for example, toaspirate fluid such as blood or particles such (e.g., see hole 988 ofFIG. 9 and accompanying text), form a treatment region of a blood vesselthrough lumen 508, and out of nozzle 520. This could be used, forexample, to aspirate a vessel distal to balloon 510, before deflatingballoon 510 so that fluid will be removed from the vessel.

According to various embodiments, guide catheter 502 may be anappropriate length for reaching a treatment region of a subject during amedical procedure, such as by having a length of between three inchesand five feet. Also, guide catheter 502, balloon 510, and ballooninflation cannula 512 may be formed of materials similar to those forforming components of system 300. Moreover, balloon inflation cannula512 may include one or more of a synthetic or natural latex or rubber,such as a polymer material; a polyetheramide; a plasticiser freethermoplastic elastomer; a thermoplastic blend; a block copolymer ofpolyether and polyester (e.g., such as a polyester sold under thetrademark Hytrel® of DUPONT COMPANY); a biocompatible polymer such as apolyether block amide resin (e.g., for instance, PEBAX® of ATOCHEMCORPORATION); a polycarbonate or acrylonitrile bubadiene styrene (ABS);a biocompatible polymer such as a polyether block amide resin; a styreneisoprene styrene (SIS), a styrene butadiene styrene (SBS), a styreneethylene butylene styrene (SEBS), a polyetherurethane, an ethylpropylene, an ethylene vinyl acetate (EVA), an ethylene methacrylicacid, an ethylene methyl acrylate, an ethylene methyl acrylate acrylicacid, a material from a material family of one of styrenic blockco-polymers and polyurethanes, a melt processible polymer, a lowdurometer material, and nylon. Likewise, balloon 510 may be attached toguide catheter 502 by processes described herein for attaching a balloonto a catheter, including by laser, adhesive, shrink tube bonding, andheat bonding.

In other embodiments, proximal end 504 of guide catheter 502 is providedwith flap 519 instead of valve device 516. Flap 519 is, for example, amaterial similar to a material for inflation cannula 512 (e.g., such asmaterials described above with respect to components of system 300, or asynthetic or natural latex or rubber, or other materials that can blockfluid flow). Flap 519 has a suitable dimensions to block off and occludelumen 508, such as to prohibit blood or treatment agent from flowingpast flap 519. Thus, flap 519 serves to close guide catheter opening 514when there are no devices disposed in or through guide catheter 502 suchas a device or cannula holding flap 519 open. For instance, flap 519 maybe attached to the inside of catheter 502 along lumen 508, at one ormore locations, by one or more of a hinge, a pin, an anchor, laserbonding, adhesive bonding, and heat bonding. Thus, when the device,catheter, or cannula (not shown) is inserted into guide catheter opening514, the device or cannula pushes flap 519 opens with some degree offorce, such as by forcing flap 519 from close position CL to openposition OP, as shown in FIGS. 5 and 6. For instance, a device,catheter, or cannula inserted into guide catheter opening 514 indirection 583 can push flap 519 from close position CL to open positionOP, as shown in FIGS. 5 and 6, and allow lumen 508 to define an openingextending from guide catheter opening 514 to distal opening 594. Afterthe device or cannula is removed from guide catheter opening 514 orpushing flap 519 open, flap 519 has a property that causes it to resistor occlude a flow of any liquid or particles flowing from lumen 508towards guide catheter opening 514. Hence, after the device or cannulais removed from pushing flap 519 open, flap 519 has a property or ismounted to close, such as by causing flap 519 to move from open positionOP to close position CL, and to be biased in closed position CL withsufficient force to stop or occlude a flow of any liquid or particlesflowing from lumen 508 towards guide catheter opening 514 Thus, whenclosed, flap 519 prevents fluid originating from opening 594 fromflowing through lumen 508 within guide catheter 502 and flowing outguide catheter opening 514.

In other embodiments, proximal end 504 of guide catheter 502 includessealing cap 530 adapted to seal guide catheter opening 514 instead ofvalve device 516 or flap 519. Sealing cap 530 serves to seal guidecatheter opening 514 such as by having threads that engage other threadsat the proximal end of guide catheter 502, or by having a recess forengaging a lip at the proximal end of guide catheter 502. Thus sealingcap 530 may be used to seal off proximal end of guide catheter 502 whenattached thereto, and may be removed from proximal end of guide catheter502 such as to aspirate a treatment region of a vessel as describedabove with respect to valve device 516. More particularly, cap 530 maybe attached to guide catheter 502 until such time as it is desired toaspirate a vessel distal to balloon 510 (e.g., such as after the balloonis inflated and before deflating the balloon). At that time, cap 530 canbe removed, and liquid from the vessel can flow from lumen 508 throughguide catheter 502 out guide catheter opening 514 and into collectionreceptacle 532.

Furthermore, according to some embodiments, catheters, such as a guidecatheter, include a filter device capable of filtering certain particlesfrom passing through the catheter but not restricting fluid flow. Forinstance, a coronary sinus access guide or catheter may have acollection cage or filter device to filter unwanted particles ormaterial from blood. For example, FIG. 7 is a side view of a cannula anda filter device in a sheath. As shown in FIG. 7, apparatus 700 includescannula 710, such as a cannula having a dimension suitable forpercutaneous advancement through a blood vessel, includes proximalsection 712 and distal end 714. FIG. 7 also shows filter device 720having proximal portion 722 axially coupled or connected to an exteriorsurface of cannula 710 at or adjacent distal end 714. For instance, aninner diameter of proximal portion 722 may be attached to an exteriorsurface of cannula 710 by laser bonding, adhesive bonding, heat bonding,or other bonding techniques at an appropriate location adjacent todistal end 714 to filter unwanted particles or material from bloodflowing in direction 784 in a treatment region, such as treatment region996.

Filter device 720 also has distal portion 724 having a first diameter D1under a first set of conditions. For example, a first set of conditionsmay include filter device 720 being restrained (e.g., to less than aninner diameter of a blood vessel into which it will be placed) by sheath790, or restricted by a retraction or contraction pressure, such as apressure resulting from a deflated balloon, tendon, or self-contractingfilter device.

Thus, as shown in FIG. 7, diameter D1 is smaller than and restrained bydiameter of the sheath DS, and is larger than diameter of the cannulaDC, forming first angle A1 between generally conical-shaped innersurface 737 and the surface of cannula 710. For example, according tosome embodiments, first angle A1 shown in FIG. 7 may be an angle between0° and 20°, such as an angle of 2°, 3°, 4°, 5°, 6°, or 10°. As a resultdistal portion 724 may have a first diameter between 1 mm and 14 mm,such as by having an outer diameter corresponding to French size 5F, 6F,7F, 8F, 9F, 10F, 12F, 15F, 18F, 24F, and 30F.

FIG. 8 is a view of FIG. 7 from perspective “A”. FIG. 8 shows conicalshape inner surface 737 at filter device 720 including proximal portion722 having a diameter approximately equal to diameter of cannula DC anddistal portion 724 having first diameter D1. FIG. 8 also shows sheath790 having diameter of sheath DS, such as a diameter of sheathsufficient to restrict or contain the diameter of distal portion 724 tofirst diameter D1. Note that although in FIGS. 7 and 8, cannula 710,proximal portion 722, distal portion 724, and sheath 790 are shownhaving side sections through line A-A′ that are approximately circular,various other closed shapes are contemplated such as an oval, a square,a triangle, a trapezoid, an ellipse, or a combination thereof.

Moreover, sheath 790 may be retracted in a proximal direction (e.g.,direction 784) so that sheath end 794 is pulled back beyond distalportion 724 allowing first diameter D1 to expand beyond a diameter ofthe sheath DS. Similarly, according to some embodiments, pull wire 792(e.g., such as a wire disposed within sheath 790 extending from distalend 714 to a proximate end of sheath 790 external to the body of asubject) may be pulled or removed, such as by being pulled in direction784, to form a seam in sheath 790 (e.g., such as where pull wire 792 wasbefore removal) so that sheath 790 may be entirely or partially removedfrom encasing cannula 710 or filter device 720. More particularly,filter device 720 may have a property such that first diameter D1 ofdistal portion 724 can be transformed, enlarged, or expanded to a seconddiameter under a second set of conditions. Consequently, first diameterD1 can be transformed to become a second diameter, such as in responseto expansion pressures 730 and 732 applied to generally conical-shapedinner surface 737.

In various embodiments, distal portion 724 has a different seconddiameter under a second set of conditions, where the second diameterapproximates an inner diameter of a blood vessel. For example, FIG. 9 isa side view of a distal end of a cannula including a filter devicehaving a distal portion with a second diameter that is approximately theinner diameter of a blood vessel at a treatment region. Specifically,FIG. 9 shows cannula 710 percutaneously advanced through blood vessel990, and sheath 790 retracted so that sheath end 794 is retracted beyondproximal portion 722 allowing filter device 720 to expand in directions786 and 788 so that distal portion 724 has different second diameter D2under the second set of conditions (e.g., retraction of sheath 790) thatis at least equivalent to inner diameter of blood vessel DV at treatmentregion 996.

Note that treatment region 996 may be a treatment region proximate towhere distal portion 724 contacts blood vessel 990, and optionallyincluded the region contained in blood vessel 990 distal to filterdevice 720 and containing distal end 714. For example, second diameterD2 may be a diameter approximately equal to the diameter of a bloodvessel at a region or point of interest, a diameter slightly less thanthat of a blood vessel at a point or treatment region, or a diameterslightly greater than that of a diameter of a blood vessel at a point ortreatment region. More particularly, second diameter D2 may be greaterthan the diameter of blood vessel 990 at a point or treatment region,such as by being in a range of between 0% and 25% larger, such as bybeing 3% larger, 5% larger, 10% larger, or 15% larger in diameter.

Specifically, filter device 720 may have a property such that firstdiameter D1 can be transformed to become second diameter D2 in responseto expansion pressures having a total of between approximately twoatmospheres in pressure and six atmospheres in pressure applied togenerally conical-shaped inner surface 737 (e.g., such as caused bypressures 730 and 732) to cause surface 737 to expand to secondgenerally conical-shaped inner surface 937. According to someembodiments, expansion pressures 730 and 732 may be the result of,applied by, or caused by, a fluid flow in direction 784. For example,expansion pressures 730 and 732 may be applied by a flow of blood 986 indirection 784 having a pressure greater than 2.0 millimeters of Mercury(mmHg) in pressure to cause distal portion 724 to expand in directions786 and 788.

Also, according to some embodiments, filter device 720 includesself-expanding materials (e.g., such as shape memory alloys, includingfor example, Nickel-Titanium) or other materials that have shape memorywhere the memorized shape is the expanded shape. To modify the shape(e.g., to restrict the shape) a sheath may be placed over filter device720. Removing the restriction will allow the shape memory material toreturn to its memorized shape (e.g., an expanded shape). Specifically,for example, filter device 720 may include a self-expanding frameportion to provide the second set of conditions under which distalportion 724 has second diameter D2.

Furthermore, according to some embodiments, filter device 720 may have aproperty, such as including a material, such that under the secondcondition (e.g., the condition described above wherein second diameterD2 approximates an inner diameter of a blood vessel) filter device 720will restrain from flowing through filter device 720 plurality ofparticles 980 having a particle size greater than an average particlesize of blood cells 982. More specifically, for example, as shown inFIG. 9, filter device 720 may restrain particles 980 (e.g., such asinfusion pellets, suspended cells, stem cells, or microspheres) in fluid986 flowing in direction 784, from flowing through filter device 720.Thus, particles having a particle size approximately that of an averageparticle size of blood cells, such as blood cells 982, contained influid 986 flowing in direction 784, may travel through filter device 720without being restrained (e.g., such as if unrestrained blood cell 983originated in treatment region 996). For example, a typical red bloodcell has a size of approximately 7 micrometers in diameter, and atypical white blood cell has a size of between approximately 7 and 15micrometers in diameter.

Consequently, according to some embodiments, filter device 720 mayinclude a material, such as material 930 having or pierced by aplurality of openings, such as openings 931 and 932, having a dimensionsuitable to allow a fluid, such as blood, to pass therethrough. Moreparticularly, openings 931 and 932 may have a dimension suitable toallow a fluid including blood cells 982 to flow through the openings andhaving a dimension suitable to restrain particles 980 having a particlesize greater than an average particle size of blood cells. For example,openings 931 and 932 may have a diameter of between 10 micrometers and100 micrometers in diameter. Thus, openings 931 and 932 may act like atrap, a sieve, or a strainer of particles to restrain particles 980.Moreover, according to some embodiments, particles, materials, andmatter restrained by filter device 720 may be restrained such as bycausing the particles, material, or matter to bond to or be coupled tofilter device 720, to rest against filter device 720, or to berestrained within the area of blood vessel 990 distal to filter device720, such as the area including distal end 714. It is contemplated thatmaterial 930 may include various suitable materials such as natural orsynthetic material, plastic, stainless steel, PEBAX 91 (a biocompatiblepolymer such as a polyether block amide resin, sold under the trademarkPEBAX® of ATOCHEM CORPORATION, PUTEAUX, FRANCE), embolic protectionmaterial, or various other appropriate filtration materials.

Material 930 may be connected or attached to a frame portion, such as bylaser bonding, adhesive bonding, thermal bonding, mechanical restriction(e.g., such as if material 930 is woven or sewn through structure orportions of the frame, such as a structure having space between piecesof the structure or holes in the frame), or various other appropriateattachment methods.

For example, filter device 720 may include a frame portion defined byproximal portion 722 and distal portion 724. According to someembodiments, an inner diameter of the frame portion may be attached toan outer surface of cannula 710, at proximal portion 722 such as bylaser bonding, adhesive bonding, thermal bonding, mechanical bonding(e.g., such as is described above for attaching material 930 to theframe portion), or various other techniques of bonding sufficient topreclude all or a portion of the inner diameter of filter device 720from becoming separated from the outer surface of cannula 710. Forexample, a sufficient attachment would preclude a portion or all of aninner diameter of filter device 720 from becoming detached from theouter surface of cannula 710 during expansion or retraction of distalportion 724, a first set of conditions, a second set of conditions,during restriction of a fluid flowing through filter device 720, orduring aspiration of particles from treatment region 996, such as isdescribed herein (e.g., see hole 988 of FIG. 9 and accompanying text).

It is contemplated that the frame portion may include one or more of aleaflet-shaped support, a helical-shaped support, a cone-shaped support,a spar-shaped support, a basket-shaped support, a ring-shaped support(e.g., to allow material 930 to form a “parachute” shape), or acombination thereof. More specifically, a frame portion may have aplurality of extending supports extending from proximal portion 722 todistal portion 724, such as a spar, a rod, a shaft, a dowel, a pull, aspine; and a plurality of cross supports disposed between the pluralityof extending supports, such as a rib, a cross-link, and a cross-wrapwrapped around, over, or under the extending support. In addition, it iscontemplated that filter device 720 or the frame portion of filterdevice 720 may include one or more of tubing, wires, ribs, ribbons,forged materials, extruded materials, cast materials, and depositedmaterials. For example, FIG. 9 shows filter device 720 havinglongitudinally disposed, circumferentially spaced elements, includingelements 920, 921, and 922. Moreover, filter device 720 may include ribsor cross supports, such as ribs 924 and 926.

Likewise, filter device 720 may include a material stretched on a frameportion to form a generally conical-shaped inner surface. For example,FIG. 10 is a view of FIG. 9 from perspective B. FIG. 10 shows proximalportion 722 having diameter of proximal portion DP and material 930stretched to form generally conical-shaped inner surface 937 betweenproximal portion 722 and distal portion 724 having second diameter D2.Thus, frame portion 720 may have material 930 on, over or underlongitudinally disposed elements or spars spaced and defining a conicalshape extending from proximal portion 722 to distal portion 724, such asis shown by conical shape 937 of FIGS. 9 and 10 or conical shape 737shown in FIGS. 7 and 8. FIG. 10 also shows blood vessel 990 havingdiameter of vessel DV which is slightly less than second diameter D2.Thus, in various embodiments, it is contemplated that second diameter D2approximates an inner diameter of a coronary sinus of a subject at atreatment region, such as by having a diameter of between 6.5millimeters and 11 millimeters. Also, material 930 may be stretched on aframe portion, such as a frame including elements 920, 921, and 922 orribs 924 and 926 to form generally conical-shaped inner surface 737under a first set of conditions and generally conical-shaped innersurface 937 under a different second set of conditions.

In addition, FIG. 9 shows generally conical-shaped inner surface 937forming second angle A2 between generally conical-shaped inner surface937 and the surface of cannula 710. According to some embodiments,second angle A2 may be an angle between 5° and 85°, such as an angle of10°, 20°, 25°, 30°, 35°, 40°, 45°, 50°, 55°, 60°, and 65°. Consequently,distal portion 724 may have second diameter D2 in a range between threemm and 15 mm, such as, an outer diameter corresponding to French size9F, 12F, 15F, 18F, 24F, 28F, 30F, 32F, and 34F.

Furthermore, according to some embodiments, distal portion 724 may havevarious cross sectional aspects or shape. Specifically, although distalportion 724 is shown in FIGS. 7 and 9 having a w-shaped profile, distalportion 724 may have various appropriate shaped profiles, such as anm-shape, a flat shape, a c-shape, an s-shape, or a shape including oneor more of the previously mentioned shapes. Likewise, elements 920, 921,and 922, as well as ribs 924 and 926 may also have various appropriateshapes, such as those described above with respect to distal portion724. Also, it is contemplated that a self-expanding or self-contractingframe may include frame structure, portions, elements, or ribs having ametallurgy with a memory, an elastic material, nitinol (NiTi), a shapedmemory alloy (e.g., such as a memory alloy that when formed to a shaperemembers or returns to that shape if not restrained or damaged). Forexample, a self-expanding or self-extracting frame may be a metal framewith a helical-spring shape, or a shape including ribs with a memory,that flexes when constrained.

Once particles are restrained, such as with the filter devicesrestraining particles, material, and matter, according to variousembodiments, filter device 720 may include a property to allowaspiration of the particles, material, and matter being restrained.Specifically, cannula 710 may include one or more holes, such as hole988 through the exterior surface of cannula 710, as shown in FIG. 9, toallow aspiration of restrained particles, such as particle 980. Thus,hole 988 may be used to aspirate or draw unwanted material, such asinfusion pellets, suspended cells, stem cells, or microspheres out ofthe treatment zone or treatment region, such as via evacuation orsuction to pull the unwanted material through hole 988 and into cannula710. For example, aspiration of restrained particles is contemplated toinclude aspiration of fluid 986, and blood cells 982, such as via asuction or vacuum provided at hole 988 provided via a cannula includinglumen 989 extending from hole 988 through cannula 710 to proximalsection 712. According to some embodiments lumen 989 may include asurrounding material, sleeve, cannula or lumen, such as described belowwith respect to infusion lumen 9520 or accessory lumen 9530 of FIGS.69A-F. Hole 988 may be located between 0.2 mm and 10 cm from the end ofdistal end 714.

Distal portion 724 may be expanded from first diameter D1 (FIGS. 7 & 8)to second diameter D2 (FIGS. 9 & 10) as a result of filter device 720being self-expanding, expansion pressure from fluid flow in direction784, or various other appropriate systems or devices, such as forapplying pressures 730 and 732. For example, FIG. 11 is a side sectionview of a filter device with a distal portion having a first diameterand balloons attached to the filter device or the cannula. FIG. 11 showsballoons 1132 and 1134 attached to filter device 720 at attachmentlocations 1139, and attached to cannula 710, such as at attachmentlocations 1129, such that inflation of balloons 1132 and 1134 (e.g.,such as inflation via cannulas as described below in FIGS. 17 and 18)transforms distal portion 724 of filter device 720 from first diameterD1 to a second diameter. According to some embodiments, the balloons maybe attached to the filter device or cannula at attachments locations1129 or 1139, such as by an adhesive, heat bonding, laser bonding,welding, or stitching.

Thus, for example, balloons 1132 and 1134 may be inflated withsufficient pressure to cause an expansion pressure as described withrespect to FIGS. 7 and 9 (e.g., such as pressure similar to thosedescribed above for pressure 730 and 732) applied to generallyconical-shaped inner surface 1137 (e.g., such as similar to conicalshape 737 described above).

Consequently, balloons 1132 and 1134 may be inflated to have a volumegreater than that shown in FIG. 11 to transform distal portion 724 fromfirst diameter D10 to a larger second diameter. For example, FIG. 12 isa side-section view of a filter device with a distal portion having asecond diameter, wherein the filter device is attached to inflatedballoons, which are attached to a cannula. FIG. 12 shows inflatedballoons 1142 and 1144 attached to filter device 720 and cannula 710(e.g., such as described above with respect to balloons 1130 and 1131)for transforming distal portion 724 of filter device 720 from firstdiameter D10 to second diameter D20. For instance, in variousembodiments, inflated balloons 1142 and 1144 may be balloons 1132 and1134 respectively, after inflation to become balloons 1142 and 1144.Note that according to some embodiments, diameter D10 may be a diametersimilar to those described above with respect to first diameter D1, andsecond diameter D20 may be a diameter similar to those described abovewith respect to second diameter D2.

Also, according to some embodiments, filter device 720 may includeanchors proximate to distal portion 724 for engaging tissue, to anchorfilter device 720, or cannula 710 to an inner diameter of a bloodvessel. For instance, FIG. 11 shows a filter device with a distalportion having anchors capable of engaging tissue of a blood vessel. Asshown in FIG. 11, anchors 1122 and 1124 proximate to distal portion 724,where anchors 1122 and 1124 include a protruding barb capable ofengaging tissue of a blood vessel, such as by piercing the innerdiameter tissue to a sufficient depth to engage a sufficient amount ofthe tissue of blood vessel 990 to prohibit and anchor from being removedfrom its engagement of blood vessel 990, such as by the flow of liquidor blood in direction 784 toward filter device 720. Moreover, anchors1122 and 1124 may be attached to elements or ribs of a frame of filterdevice 720 such as element 922 and rib 926 of FIG. 9. Thus, anchors 1122and 1124 may be extended in directions 786 and 788 as shown in FIG. 11,to engage tissue of blood vessel as shown in FIG. 12. Consequently,anchors 1122 and 1124 may be disengaged from tissue of blood vessel 990such as by retraction of distal end 724 or by moving filter device 720in direction 985. Hence, anchors 1122 and 1124 may be disengaged fromtissue, such as by retracting or contracting distal portion 724 to moveanchors 1122 and 1124 in directions 1186 and 1188 as shown in FIG. 12.

For instance, filter device 720 may have a property such that seconddiameter 1120 can be transformed to become or constrict to approximatelyfirst diameter D10 in response to a retraction or contraction pressuresuch as shown by pressures 1140 and 1141 of FIG. 12. According to someembodiments, sufficient retraction pressure may be in the range ofbetween approximately two atmospheres in pressure and 35 atmospheres inpressure applied to generally conical-shaped inner surface 1138. Moreparticularly, as shown in FIG. 12, balloons 1142 and 1144 attached tofilter device 720 and cannula 710 may be deflated (e.g., such as vialumens as described below with respect to FIGS. 17 and 18) to transformdistal portion 724 of filter device 720 from second diameter D20approximately to first diameter D10. For example, FIG. 13 is a sidesection view of a filter device with a distal portion having a thirddiameter, where the filter device is attached to deflated balloons whichare attached to a cannula. FIG. 13 shows deflated balloons 1152 and 1154attached to filter device 720 (e.g., as described above with respect toattachment at attachment locations 1139) and attached to cannula 710(e.g., such as described above with respect to attachment at attachmentlocations 1129) such that distal portion 724 is transformed to thirddiameter D30. For instance, in various embodiments, deflated balloons1152 and 1154 may be balloons 1132 and 1134 respectively, afterinflation and deflation (e.g., such as after inflation of balloons 1132and 1134 to become balloons 1142 and 1144, and deflation of balloons1142 and 1144 to become balloons 1152 and 1154).

Therefore, for example, inflated balloons 1142 and 1144 may be deflatedto cause pressures 1140 and 1141 sufficient to create a retractionpressure as described above, applied to generally conical-shaped innersurface 1138, thereby retracting distal portion 724 to directions 1186and 1188 from second diameter 1120 to third diameter D30 as shown inFIG. 13, which may be a diameter in a range of between 100 percent and130 percent of D10.

FIG. 14 is a side view of a distal portion of a cannula including afilter device having a distal portion attached to tendons which pivot ata pivot point and extend through a cannula. As shown in FIG. 14, filterdevice 720 includes tendons 1430 and 1440 which extend from proximalsection 712 of cannula 710 to pivot points 1432 and 1442 and then areattached to distal portion 724, such as via attachment at attachmentlocations 1439. Note that attachment attachment locations 1439 may be anattachment achieved such as is described with respect to attachment atattachment locations 1139 and 1129. Tendons 1430 and 1440 may extendfrom proximal section 712 of cannula 710 to pivot points 1432 and 1442,such as via lumens as described below in FIGS. 17 and 18. Thus, tendons1430 and 440 may be actuated such as by releasing tension or extendingthe tendons in direction 985 to transform distal portion 724 from firstdiameter D11 to a second diameter (e.g., such as a result of anexpansion pressure similar to those described above with respect toFIGS. 7-13 and pressures 730 and 732 applied to generally conical innersurface 1437). It is contemplated that generally conical inner surface1437 may be similar to conical shape 737 as described above. It is alsoto be appreciated that tendons 1430 and 1440 may extend through proximalsection 712 such as to exit a proximal portion of cannula 710 exteriorto the body of a subject so that tendons 1430 and 1440 may be locked ina locking position. More particularly, tendons 1430 and 1440 may extendthrough a tendon port similar to port 398 above (see FIG. 3 andaccompanying text) and be locked in a locking position, such as by alocking mechanism disposed within a proximal portion of cannula 710, atendon port, or external to the tendon port. Hence, tendons 1430 and1440 may be retained in their locking position until it is desired toactuate them as described above. Moreover, after actuation of tendons1430 and 1440 as described above, the tendons may be manipulated, orretracted as described below and returned to a locking position, such astheir original locking position before actuation.

Moreover, tendons 1430 and 1440 may be of various suitable materialssuch as natural or synthetic fiber, plastic, stainless steel or variousother appropriate metals. Likewise, pivot points 1432 and 1442 may behard points such as a point where the tendon exits cannula 710 or alumen as described below with respect to FIGS. 17 and 18. Moreover pivotpoint 1432 and 1442 may contain various appropriate pivot structuressuch as a curved surface, a hard point, an exit hole of an inflationlumen, an exit of a lumen such as lumens described below in FIGS. 17 and18, or an aspiration hole such as hole 988 (see FIG. 9 and accompanyingtext), or a small wheel.

For example, FIG. 15 is a side section view of a filter device with adistal portion having a second diameter, wherein the filter device isattached to tendons which extend through a cannula. FIG. 15 showsactuated or released tendons 1450 and 1460 attached or coupled to distalportion 724 and cannula 710 (e.g., such as described below in FIGS. 17and 18) for transforming distal portion 724 from first diameter D11 tosecond diameter D21. Note that according to some embodiments, diameterD11 may be a diameter similar to those described above with respect tofirst diameter D1 (see FIG. 7 and accompanying text), and seconddiameter D21 may be a diameter similar to those described above withrespect to second diameter D2.

Actuated or released tendons 1450 and 1460 may be manipulated, such asby retracting or pulling tendons 1450 and 1460 in direction 784 to movedistal portion 724 in directions 1186 and 1188 to transform seconddiameter D21 into a third diameter, such as a diameter approximatelyequal to first diameter D11. For example, FIG. 16 is a side section viewof a filter device with a distal portion having a third diameter andtendons attached to the distal portion and extending through a cannula.As shown in FIG. 16, reactuated or pulled tendons 1470 and 1480 areattached to distal portion 724, pivot at pivot points 1432 and 1442, andextend through cannula 710, such that distal portion 724 is transformedto third diameter D31. It is contemplated that third diameter D31 may bea diameter similar to those described above with respect to thirddiameter D30.

Suitable actuation or manipulation tension for tendons 1430 and 1440includes a range of tension between for example, zero pounds and fivepounds such as a suitable tension for causing or countering an expansionpressure (e.g., such as caused by pressures 730 and 732) and orretraction pressure (e.g., such as described by pressures 1140 and 1141)as described above.

According to some embodiments, distal portion 724 may also be retractedfrom the second diameter to approximately the first diameter by variousother appropriate designs or systems including a self contracting filterdevice, such as using materials similar to the self expanding filterdevice described above, but having an opposite transformation principle.Likewise, distal portion 724 may be retracted by a sheath such as sheath790. Specifically, as shown in FIG. 9, sheath 790 may be moved indirection 985, to retract and cover over filter device 720 such as wherethe force of sheath moving in a distal direction causes retraction ofdistal portion 724. Specifically, sheath 790 may be moved in direction985 of FIG. 9 until the configuration of FIG. 7 is accomplished (e.g.,with sheath 790 over distal portion 724 of filter device 720).

Besides the above descriptions of retracting the second diameter ofdistal portion 724, it is contemplated that filter device 720 can beremoved from blood vessel 990 without retraction of the second diameter.For example, distal portion 724 may have a property such that it can beretracted in direction 784 along blood vessel 990 without damaging orbreaching blood vessel 990. Specifically, distal portion 724 may haveatraumatic tips (e.g., such as by having properties at second diameterD2 as shown in FIG. 9, or atraumatic tips instead of anchors 1122 and1124 at positions shown in FIG. 12) such that filter device 720 can beretracted in direction 784 while having second diameter D2 or seconddiameter D20 under a second set of conditions. The tension on distalportion 724 is such that second diameter D20 may fluctuate (constrain orexpand) as filter device 720 moves through one or more blood vessels.

Note that FIG. 14 also shows third angle A3 formed between tendon 1430extending through lumen 710 and a point at which tendon 1430 is attachedor coupled to distal portion 724. For example, according to someembodiments, third angle A3 shown in FIG. 14 may be an angle between 10°and 210°, such as an angle of 45°, 60°, 70°, 80°, 90°, 100°, 120°, and125°.

According to some embodiments it is possible to mix technologiesdescribed above with respect to restraining distal portion 724 by aretraction or contraction pressure, expanding distal portion 724 by anexpansion pressure, or retracting distal portion 724 by a retraction orcontraction pressure. For example, it is possible for filter device 720and cannula 710 to include a self expanding filter device, or balloonexpanded filter device, restrained by tendons, wherein the distalportion of filter device 720 may be expanded to a second diameter byself expansion or inflation of the balloons as described above, and thenretracted to a third diameter by deflation of the balloons ormanipulation of the tendons as described above. Likewise, it is possiblefor filter device 720 and cannula 710 to include a self expanding filterdevice, or balloon expanded filter device, restrained by a sheath,wherein the distal portion of filter device 720 may be expanded to asecond diameter by self expansion or inflation of the balloons asdescribed above, and then retracted to a third diameter by deflation ofthe balloons or manipulation of tendons attached to the distal portion,as described above.

FIG. 17 is a front cross sectional view of the filter device of FIG. 9showing a proximal portion of the filter device axially attached to anexterior surface of a cannula and lumens extending through the cannula.As shown in FIG. 17, filter device 720 has distal portion 724 andproximal portion 722 attached to an exterior surface of cannula 710. Forexample, in embodiments, FIG. 17 may be a front cross sectional view ofa filter device and cannula from perspective “A” of FIG. 12 or 15. FIG.17 also shows lumens 1712, 1714, 1716, and 1718 extending within cannula710, such as to extend from proximal section 712 of cannula 710 to apoint distal to proximal portion 722 of filter 720 (See FIGS. 7, 9, and11-16, and accompanying text). In addition, lumen 1740 is shownextending along inner surface of cannula 1722 from proximal section 712of cannula 710 to a point distal to proximal portion 722 of filter 720.It is to be appreciated that lumens 1712, 1714, 1716, 1718, or 1740 mayexit cannula 710 through exit holes or openings in the proximal end,distal end, or exterior of cannula 710, similar to how inflation lumen9540 extends from proximal end 9504 to balloon 9510 and exits aninflation opening within balloon 9510, as described below with respectto balloon inflation lumen 9540 of FIGS. 69A-F. For example, lumens1712, 1714, 1716, 1718, or 1740 may be lumens sufficient for passinginflation gas or fluid through, such as for inflating and deflatingballoons 1132, 1134, 1142, or 1144 as described above (see FIGS. 11-13and accompanying text). Also, lumens 1712, 1714, 1716, 1718, or 1740 mayhave a pivot point as any hole or opening where a lumen exits cannula710, such as by having pivot point 1432 or 1442 at an opening where thelumen exits the exterior surface of cannula 710. Likewise, lumens 1712,1714, 1716, 1718, or 1740 may be lumens sufficient for extending,acuating, releasing, extending, manipulating, or pulling tendons 1430,1440, 1450, or 1460 therethrough (see FIGS. 14-16 and accompanyingtext). Specifically, lumen 1712 is shown in FIG. 17 with tendon 1730extended therethrough (e.g., tendon 1730 may be a tendon such as tendon1430, 1450, or 1470).

Furthermore, lumens described herein, such as lumen 1712 and lumen 1714may provide for aspiration of particles, material, and matter asdescribed above with respect to hole 988 (e.g., see FIG. 9 andaccompanying text). Moreover, lumens 1712, 1714, 1716, 1718, or 1740 maybe include a surrounding material, sleeve, cannula or lumen, such asdescribed below with respect to infusion lumen 9520 or accessory lumen9530 of FIGS. 69A-F

In addition, according to some embodiments, any or all of lumens 1712,1714, 1716, 1718, or 1740 may be used to inflate or deflate a balloon(e.g., such as balloons 1132, 1134, 1142, or 1144 as described abovewith respect to FIGS. 11-13 and accompanying text) as well as have atendon extending therethrough (e.g., such as for acuating, releasing,extending, manipulating, or pulling tendons 1430, 1440, 1450, or 1460therethrough as described above with respect to FIGS. 14-16 andaccompanying text). Specifically, for example, lumen 1712 may be usedfor inflating and deflating balloons as described herein, as well as forhaving a tendon for actuation or manipulation as described herein,extending therethrough.

Note that it is contemplated that balloons described herein will beinflated and deflated using fluids, including fluids described herein asa treatment agent. Likewise, it is also contemplated that lumensdescribed herein, such as lumen 1712 and 1714, may provide thecapability to inflate or deflate occlusion devices and balloons, tocontain tendons, to contain guide wires, to provide for delivery oftreatment agent, to provide for aspiration of treatment agent orparticles, or to provide for pressure release, such as by providingthose capabilities for filter 720, devices other than filter 720, or atvarious regions of interest other than treatment region 996. Thus,balloons 1132, 1134, 1140, 1141, 1152, and 1154 (See FIGS. 11-13, andaccompanying text), as well as lumens 1712, 1714, 1716, 1718, and 1740may contain and provide sufficient pressure of a fluid, including atreatment agent, to inflate and deflate balloons as described herein.

Although FIG. 17 shows four lumens extending through cannula 710,according to some embodiments, any number of lumens may be associatedwith cannula 710, filter device 720 other devices, or regions ofinterest as described herein. Constraints on the number of lumens thatmay be associated with cannula 710, include the number lumen or cannulanecessary for a particular purpose and the overall size (e.g, inner orouter diameter) of a system for delivery of a treatment agent to atreatment region. For example, in an embodiment where filter device 720has a helical spring shape, three lumen may be associated with cannula710 to restrain, actuate, manipulate, or extend distal portion 724 ofthe filter device. More particularly, FIG. 18 is a front cross sectionalview of a filter device having a proximal portion axially attached to anexterior surface of a cannula, wherein the filter device has a helicalspring shape. FIG. 18 shows filter device 720 having proximal portion722 axially attached to an exterior surface of cannula 710, whereinfilter device 720 includes helical spring shape 1820. Helical springshape 1820 may provide filter device 720 with a self-expanding frame, aself-contracting frame, or a frame portion (e.g., such as for havingmaterial stretched on the frame) as described herein. FIG. 18 also showslumens 1812, 1814, and 1818 extending along the outer surface of cannula710 from proximal section 712 of cannula 710 to a point distal toproximal portion 722 of filter 720. Lumens 1812, 1814, or 1818 may be alumen such as is described above with respect to lumen 1712.

The various configurations of filter device 720 and lumen 710 describedherein can be used to restrain and aspirate particles, material, andmatter as described above for a variety of catheters, including guidecatheters, delivery catheters, guide wires, and other cannula. Forexample, FIG. 19 is a flow diagram of a process for using a filterdevice to restrain and aspirate particles. At block 1910 a cannula, suchas cannula 710, is advanced percutaneously through a blood vessel, suchas blood vessel 990, wherein the cannula includes an exterior surface ator adjacent a distal end of the cannula axially coupled or connected toa proximal portion of a filter device, such as filter device 720. It iscontemplated that the cannula may be advanced via a retrogradeadvancement, such as by being pushed up or down a blood vessel (e.g.,such as a blood vein or artery) against or with a flow of blood.Specifically, the cannula may be advanced, such as from one blood vesselinto a smaller blood vessel to provide retrograde infusion treatment, toa treatment region such as a region in a coronary sinus of a subject.

At block 1920, the distal diameter of a filter device, such as firstdiameter D1, is transformed or enlarged to a different second diameter,such as second diameter D2, that is approximately equivalent to an innerdiameter of a blood vessel at a treatment region, such as diameter ofvessel DV of blood vessel 990 at treatment region 996. For example,first diameter D1 may be expanded in directions 786 and 788 to seconddiameter D2 until second diameter D2 approximates an inner diameter of acoronary sinus of a subject at a treatment region. Moreover, it iscontemplated that second diameter D2 may be expanded sufficiently tomake a pressure wave form in the blood vessel or coronary sinus becomeventricularized.

At block 1930 particles, material, or matter may be restrained fromflowing through the filter device, such as by restraining a plurality ofparticles having a particle science greater than an average particlesize of blood cells contained in blood flowing through the filterdevice. Thus, after block 1920, it is contemplated that a liquidincluding a drug, treatment agent, infusion pellets, suspended cells,stem cells, microspheres, or other drugs or treatment agent mentionedherein may be delivered or infused through a lumen extending fromproximal section 712 of cannula 710 to treatment region 996 (e.g., totreat vessel 990 at treatment region 996). During or after delivery ofthe liquid, particles, material, or matter, such as described above, aswell as stem cells, microspheres, metal, particles from devices, piecesof tissue, or other drugs or treatment agents mentioned herein may berestrained by the filter device, such as is described above with respectto filter device 720.

For instance, in various embodiments, at block 1935 a treatment agentmentioned herein is infused to a treatment region of a blood vessel,such with respect to FIGS. 3, 63, 69A-70, and 82. Specifically, atreatment tagent may be infused to a treatment region via a deliverycatheter disposed through a lumen extending from proximal section 712 todistal end 714 of cannula 710, and extending to a region of a bloodvessel.

At block 1940 the restrained particles are aspirated. For example, aplurality of particles being restrained, such as particles 980, can beaspirated proximate to the exterior surface of cannula 710, such as isdescribed above with respect to hole 988 proximate to distal end 714 orlumen 1712 (e.g., see FIG. 9 and accompanying text). It is contemplatedthat aspirating may occur during delivery of liquid or after delivery ofliquid as described above at block 1930.

At block 1950 the distal diameter of the filter device is contracted.For example, second diameter D2 may be contracted or retracted to adiameter that is approximately that of first diameter D1 (e.g., such asthird diameter D30, or D31 as described above) in response to aretraction pressure (e.g., such as pressure 1140 and 1141, or 1451 and1461).

At block 1960 the cannula and attached filter device are retracted, suchas by retracting or withdrawing the cannula back out of vessel 990 andout of the subject. For example, as noted above, it is contemplated thatcannula 710 and filter device 720 may be retracted without modifyingdistal portion 724 of filter device 720 (e.g., to leave distal portion724 at second diameter D2), or may be retracted or removed from thesubject after transforming or contracting second diameter D2 to becomeapproximately the first diameter (e.g., block 1950).

Note that according to some embodiments, the process for using filterdevice 720 to restrain and aspirate particles shown and described abovefor FIG. 19 may also apply for an apparatus similar to apparatus 700 asshown in FIGS. 7-18, but having an occlusion device or balloon attachedto cannula 710 instead of and at the location of filter device 720.Specifically, the process for using filter device 720 of FIG. 19 mayhave an occlusion device or balloon, instead of filter device 720,enlarged at block 1920 and restraining particles and fluid at block1930, by occluding the blood vessel, such as is shown and described withrespect to balloon 308 of FIGS. 3A, 3B, and 4. It can be appreciatedthat the other blocks of FIG. 19 also apply to a process having anocclusion device or balloon in place of filter device 720.

Referring now to FIG. 20, there is illustrated a guide catheter. Guidecatheter 2000 has distal end 2002 and proximal end (not shown). Adjacentdistal end 2002 is occlusion device 2006. Occlusion device 2006 may beprovided with self-expanding frame 2010, and material 2012 stretchedbetween frame structure or portions. Frame 2010 may be made of anelastic material or a superelastic material, for example, nitinol orNiTi, wherein NiTi or a material described above with respect to formingthe frame portion of filter device 720. For example, guide catheter 2000may be a guide catheter as described herein, such as cannula 710described for FIG. 7 above, and frame 2010 may be a framed portion suchas described above with respect to filter 720 described for FIG. 7.Moreover, in various embodiments, material 2012 may act as an occlusiondevice, such as by having no holes through it, or having a property suchthat fluid does not flow through it. For example, material 2012 mayinclude one or more of a synthetic or natural latex or rubber, such as apolymer material; a polyetheramide; a plasticiser free thermoplasticelastomer; a thermoplastic blend; a block copolymer of polyether andpolyester (e.g., such as a polyester sold under the trademark Hytrel® ofDUPONT COMPANY); a biocompatible polymer such as a polyether block amideresin (e.g., for instance, PEBAX® of ATOCHEM CORPORATION); apolycarbonate or acrylonitrile bubadiene styrene (ABS); a biocompatiblepolymer such as a polyether block amide resin; a styrene isoprenestyrene (SIS), a styrene butadiene styrene (SBS), a styrene ethylenebutylene styrene (SEBS), a polyetherurethane, an ethyl propylene, anethylene vinyl acetate (EVA), an ethylene methacrylic acid, an ethylenemethyl acrylate, an ethylene methyl acrylate acrylic acid, a materialfrom a material family of one of styrenic block copolymers andpolyurethanes, a melt processible polymer, a low durometer material,nylon, and other materials that can block fluid flow.

Sheath 2004, for example, a retractable or a tear-away sheath, such assheath 790, is shown pulled away from occlusion device 2006 in directionof arrow 2014. When guide catheter 2000 is deployed into a vessel (e.g.,such as is described above with respect to deployment of cannula 710 forFIG. 7, and including a blood vessel of a subject or fluid flow 2020occurs in direction of arrow 2014.

Distal end 2005 of sheath may be covering occlusion device 2006. Afterdistal end 2002 of catheter is located in a preferred location, sheath2004 may be moved in a proximal direction (e.g., a direction of arrow2014) to uncover occlusion device 2006. Thereafter, self-expanding frame2010 forces open device 2006 in direction of arrows 2018 so thatocclusion device 2006 occupies substantially the entire vessel. Anyfluid flowing through vessel in direction of arrows 2020 must then passthrough material 2012, or be trapped by material 2012.

In another embodiment, if guide catheter is placed in a vessel withfluid flow in the direction of arrow 2022, then occlusion device 2006may be turned around so that opening 2024 of occlusion device 2006 facesinto the direction of fluid flow (e.g., see arrow 2022). Therefore,frame 2010 and fluid flow 2020 or 2022 serve to force occlusion device2006 against the interior walls of a vessel (not shown). Aspirationside-hole 2016 may be provided adjacent distal end 2002 in guidecatheter 2000 such as at a location and to function as is describedabove with respect to hole 988 for FIG. 9 (e.g., distal to a proximalend of occlusion device 2006). Thus, aspiration side-hole 2016 may beused to aspirate fluid or particles from a vessel distal to device 2006.

Referring now to FIG. 21, there is illustrated a telescoping guidecatheter system. Telescoping guide catheter system includes outer guidecatheter 2100 having proximal end (not shown) and distal end 2101. Outerguide catheter 2100 has an inner diameter adapted to contain inner guidecatheter 2102, for example, the outside diameter of inner guide catheter2102 is smaller than the inside diameter of outer guide catheter 2100,so that outer guide catheter 2100 and inner guide catheter 2102 may beslidingly engaged. Inner guide catheter 2102 has proximal end (notshown) and distal end 2103. Outer guide catheter 2100 is provided withocclusion device 2104 at distal end 2101, and inner guide catheter 2102is provided with occlusion device 2112 at distal end 2103.

As illustrated, occlusion device 2104 includes frame 2106, for example,an elastic frame, and material 2108 stretched between structure orportions of frame 2106. For example, frame 2106 may have a similarstructure, functionality, and material as that described above for frame2010 of FIG. 20. Likewise, material 2108 may have a similar structure,functionality, and material as that described above for material 2012 ofFIG. 20. There may also be provided a sheath (not shown) to coverocclusion device 2104 until such time as it is to be deployed, and thesame or a different sheath may be used for device recovery. Catheter2102 may also include aspiration side-hole 2110 at distal end 2101,which may be used to aspirate fluid or particles distal to occlusiondevice 2104, such as at a location and to function as is described abovewith respect to hole 988 for FIG. 9. In FIG. 21, occlusion device 2112is shown as balloon 2112, which may be any type of balloon or occlusiondevice such as occlusion device 2006, or may be filter device such asfilter device 720.

Inner guide catheter 2102 has first curve 2114, and outer guide catheter2100 has second curve 2116. For example, according to some embodiments,first curve 2114 may be an angle between 10° and 125°, such as an angleof 10°, 20°, 30°, 45°, 60°, 80°, 90°, 100°, 120°, and 125°. Also,according to some embodiments, second curve 2116 may be an angle between10° and 90°, such as an angle of 10°, 15°, 20°, 25°, 35°, 45°, 60°, 70°,80°, and 90°. By sliding inner guide catheter 2102 back and forth indirection of arrows 2118 within outer guide catheter 2100, and rotatingouter guide catheter 2100 or inner guide catheter 2102, distal end 2103may be steered and tracked through a vessel network.

Note that according to some embodiments proximate end 712 of FIG. 7, aproximate end of guide catheter 2000, or a proximate end of guidecatheter 2100 may be attached to or extend to a guide catheter proximateportion, such as a proximate portion similar to proximate portion 305 ofFIG. 3, and having the necessary holders, tracks, cannulas, lumens, andports to provide for the functionality of cannula 710 of FIG. 7, guidecatheter 2000, or guide catheter 2100, or any other guide catheter asdescribed herein.

Referring now to FIGS. 22 and 23, there is illustrated the distal endand proximal end of a balloon catheter. Balloon catheter 2200 may be adelivery or infusion catheter having distal end 2202 and proximal end2203. Adjacent distal end 2202 of catheter is first balloon 2204. Firstballoon inflation cannula 2206 has a lumen there through and distal endincluding first opening 2208 within first balloon 2204 to inflate ordeflate first balloon 2204. There is also provided second balloon 2250,with second balloon 2250 distal to first balloon 2204. First balloon2204 or second balloon 2250 may be made of various appropriate naturalrubber, polymer, lined ePTFE, thermoplastic blend, copolymer materials,having various appropriate dimensions, and being attached to ballooncatheter 220 by various procedures (e.g., such as laser bonding,adhesive bonding, or heat bonding) as described herein.

First balloon 2204 may be a distance from second balloon 2250 sufficientto block a proximal and a distal end of a treatment region, such as aregion for delivering a treatment agent. For example, distance Ddefining a region for delivering a treatment agent between first balloon2204 and second balloon 2250 may be a distance in the range between onecentimeter and 20 centimeters, such as a distance of 10 centimeters.

Moreover, according to some embodiments, first balloon 2204 or secondballoon 2250 may have a maximum inflated outer diameter of between twomillimeters and 15 millimeters, such as by having an outer diameterduring inflation of 10 millimeters. Furthermore, according to someembodiments, first balloon 2204 or second balloon 2250 may employ awedge or conical tapered shape, such as a shape having a tapered outerdiameter towards distance D of four millimeters and an increasingdiameter to a maximum diameter away from distance D of 10 millimeters.Thus it is possible to select balloons having a tapered profile topromote better sealing of a treatment region in a vessel as well asbetter centering of the balloons upon inflation. Likewise, the size andshape of first balloon 2204 and second balloon 2250 may be selected toprovide a treatment region that may be pressurized, such as by apressurized infusion of treatment agent as described herein, whilepreventing the flow of infused treatment agents out of the treatmentregion. For example, second balloon 2250 can be selected to prevent theflow of treatment agents out of a treatment region, such as definedwithin a blood vessel along distance D, while first balloon 2204 can beselected to prevent the backflow of infused treatment agents out of thetreatment region and towards proximal end 2203. Next, the size, shape,and material of first balloon 2204 and second balloon 2250 may beselected to establish a desired pressure gradient within a vessel at thelocation of proximate to or between first balloon 2204 and secondballoon 2250. More particularly, size, shape, material, and inflationpressure of first balloon 2204 and second balloon 2250 may be selectedsuch that a treatment region as defined by distance D within a vesselmay be pressurized, such as with a treatment agent, to a pressurebetween one and 30 atmospheres (e.g., such as to a pressure of betweensix and eight atmospheres).

First balloon 2204 and second balloon 2250 may be the same shape, size,or material, or first balloon 2204 may have a different shape, size, ormaterial than second balloon 2250. Second balloon inflation cannula 2256has a lumen there through and includes distal end and second opening2258 within second balloon 2250 to inflate or deflate second balloon2250. In another embodiment, first balloon inflation lumen 2206 andsecond balloon inflation cannula 2256 are the same lumen, with twoopenings 2208 and 2258, while in another embodiment (as illustrated),first balloon inflation lumen 2206 is different than and not connectedto second balloon inflation cannula 2256.

Pressure-sensing cannula 2210 has distal end and pressure sensingopening 2212, which enables pressure-sensing, such as via a pressuresensing device with respect to fitting 2548, or other measurements orparameters to be taken in a region of a vessel between first balloon2204 and second balloon 2250, or where ever distal end 2202 is placed.Delivery cannula 2214 has distal end and delivery opening 2216 whichenables a fluid or treatment agent path from proximal end 2203 ofballoon catheter 2200 to opening 2216 between first balloon 2204 andsecond balloon 2250.

In various embodiments, balloon catheter 2200 has a tapered tip. Taperedtip of catheter 2200 may enable easier tracking of distal end 2202 ofcatheter through a blood vessel. In various embodiments, distal end 2202may have tapered cut 2222, which may be curved to have the profile shownin FIG. 22. Other configurations of distal ends 2202 are envisionedwhich would ease tracking through a blood vessel. For example, taperedcut 2222 may be at angle “A” with respect to the longitudinal axis ofcatheter 2200, where angel “A” may be an angle between 10° and 90°, suchas an angle of 10°, 15°, 20°, 25°, 35°, 45°, 60°, 70°, 80°, and 90°.Also, tapered cut 2222 may have or form a tapered shape with respect tothe longitudinal axis of catheter 2200, where the tapered shaped mayinclude one or more of a convex, a concave, and a three dimensionallyshaped cut. Thus, tapered cut 2222 can have angle “A” and a taperedshape sufficient to allow balloon catheter 2200 to be fed through avessel such as is described above with respect to feeding guide catheter302 through a vessel; or to be fed through another catheter such asguide catheter 302 or 502, such as is described above with respect todelivery catheter 310 being fed through guide catheter 302. Ballooncatheter 2200 may have an outer diameter or outer dimension to fitwithin a guide catheter such as guide catheter 302 or guide catheter502. For example, balloon catheter 2200 may have an outer diameter ofbetween 5 French and 6 French and be capable of fitting within a guidecatheter having an outer diameter of between 8 French and 9 French.

Balloon catheter 2200 may have one or more radio-opaque markers appliedto its outer diameter, such as by adhesive, laser bonding, or heatbonding, or may include a filler such as barium sulfate added to thepolymeric material used to form balloon catheter 2200 near distal end2202 to track the position of distal end 2202. According to someembodiments, such markers or filler may have various widths such as awidth between one millimeter and two centimeters, and may extend arounda portion of or completely around the circumference of balloon catheter2200.

For example, catheter 2200 may also include marker 2230, for example, aradio-opaque marker, which may serve to ease visualization of distal end2202 of catheter 2200 with a diagnostic visualization system. There mayalso be provided a second marker (not shown) adjacent second balloon2250, so that first marker 2230 and second marker (not shown) may beused to locate first balloon 2204 and second balloon 2250, respectively.

Catheter 2200 may also include guidewire cannula 2242 to extend fromproximal end 2203 through catheter 2200 to guidewire opening 2243.Guidewire cannula 2242 has distal end and guidewire opening 2243,adjacent distal end 2202 of catheter 2200. Guidewire cannula 2242 hasdimensions to receive guidewire 2244. Guidewire 2244 is illustrated,where guidewire 2244 has distal end 2246 and occlusion device 2248attached to guidewire 2244 adjacent guidewire distal end 2246. Occlusiondevice 2248 may be attached to guidewire 2244 by various appropriatemethods including laser bonding, adhesive bonding, thermal bonding andother bonding processes for attaching an occlusion device, such as aballoon, to a guidewire or catheter. In addition, balloon catheter 2200and guide catheter 1002 may have a length such as is described abovewith respect to the length of guide catheter 302.

FIG. 23 also shows first balloon inflation cannula 2206 attached tofirst balloon inflation port 2290, such as via adhesive bonding, heatbonding, threaded bonding or various other appropriate bonding processesfor attaching first balloon inflation port 2290 sufficiently so that anappropriate volume and pressure of liquid may pass therethrough toinflate first balloon 2204. Likewise, second balloon inflation cannula2256 is attached to second balloon inflation port, such as is describedabove with respect to first balloon inflation port 2290. Pressuresensing cannula 2210 is attached to pressure sensing port 2294 similarto methods described above for attaching port 2290 to cannula 2206, andsufficiently to allow a volume in pressure of fluid to float throughpressure sensing port 2294, such as to a pressure sensing deviceattached to pressure sensing port 2294, such as is described herein withrespect to a pressure sensing device with respect to fitting 2548. Next,delivery cannula 2214 is attached to delivery port 2296, such as isdescribed above with respect to attachment of port 2290 to cannula 2206,and sufficiently for delivery of a volume and pressure of a liquid ortreatment agent and to a treatment region, to provide a treatment ortreatment region as described herein. Finally, guidewire cannula 2242 isattached to guidewire port 2298, similarly to the attachment describedabove for attaching port 2290 to cannula 2206, and sufficiently so thatguidewire 2244 can extend through guidewire port 2298 and can bemanipulated, controlled, and used to place guidewire distal end 2246 orocclusion device 2248 at a desired region within a vessel as describedherein.

FIG. 24 shows a section view of FIG. 23 through line D-D′. As shown inFIG. 24, first balloon inflation cannula 2206, second balloon inflationcannula 2256, pressure sensing cannula 2210, delivery cannula 2214, andguidewire cannula 2242 are shown disposed through balloon catheter 2200such as from proximal end 2203 to distal end 2202. Furthermore,guidewire 2244 is shown fed through or disposed through guidewirecannula 2242, such as is described above. In another embodiment,guidewire and guidewire lumen (not shown) are in a monorail or OTWconfiguration. It is also contemplated that the guidewire and guidewirelumen (not shown) can te in a rapid-transfuser type configuration, suchas illustrated in FIGS. 3 and 37, and described in accompanying text.

FIG. 25 illustrates a catheter system. Catheter system 2500 includesdelivery catheter 2520 having flexible shaft 2522, distal end 2524,proximal end 2526, with a delivery lumen extending therebetween. Forinstance, delivery catheter 2520 or any delivery catheter may have adistal end has an outer diameter less than about 10 mm, seven mm, fivemm or three mm. In addition, according to some embodiments, deliverycatheter 2520 or any delivery catheter may have a flexible shaft made ofa bio-compatible polymer, a bio-compatible polymer having a durometerhardness of about 30 to about 100 shore D, a bio-compatible polymerhaving a durometer hardness of about 50 to about 70 shore D, a polyetherblock amide resin, or a flexible shaft that is radiopaque. Soft tip 2530is bonded to distal end 2524 of shaft 2522. The delivery lumen extendsfrom fitting 2532 at proximal end 2526 through shaft 2522 and throughsoft tip 2530 to outlet port 2592 in soft tip 2530. Note that a deliverylumen may have cross-sectional area suitable for advancing into acardiovascular system of a patient and to deliver a treatment agent to atreatment region in a blood vessel of the patient. Suitablecross-sectional areas include at least about 0.95 mm², 2 mm², 3 mm², 5mm², or 10 mm². One or more side holes in communication with thedelivery lumen may also be provided near distal end 2524 of shaft 2522.Pressure increasing device 2560 is shown attached to fitting 2532.

Catheter 2520 is provided with balloon 2547 on distal end 2524 ofcatheter 2520, which balloon 2547 is adapted to occlude the coronarysinus or another vessel when inflated. An inflation lumen extendsthrough shaft 2522 and is in communication with the interior of balloon2547 through opening 2537. Specifically, the inflation lumen, or anyother inflation lumen may be a balloon inflation lumen within a flexibletube or cannula shaft (e.g., such as a lumen having a surroundingmaterial, sleeve, cannula or lumen, such as described below with respectto infusion lumen 9520 or accessory lumen 9530 of FIGS. 69A-F). Nearproximal end 2526, the inflation lumen is connected to inflationextension tube 2538 attached to shaft 2522 having fitting 2540 at itsproximal end shown attached to inflation device 2564. Optionally,pressure release valve 2541 may be connected to inflation extension tube2538 to prevent over inflation of balloon 2547. Extension tube 2538 mayhave a surrounding material, sleeve, cannula or lumen, such as describedbelow with respect to infusion lumen 9520 or accessory lumen 9530 ofFIGS. 69A-F.

A pressure lumen is also provided in shaft 2522 which opens at pressureport 2544 on side-wall of shaft 2522 near distal end 2524, or in softtip 2530 as illustrated. The pressure lumen is connected to extensiontube 2546 attached to shaft 2522 near proximal end 2526. Extension tube2546 has fitting 2548 at its proximal end shown connected to pressuremeasuring device 2562. Extension tube 2546 may have a surroundingmaterial, sleeve, cannula or lumen, such as described below with respectto infusion lumen 9520 or accessory lumen 9530 of FIGS. 69A-F.

Pressure increasing device 2560 is shown connected by connection 2572 tocontroller 2570. Pressure measuring device 2562 is shown connected tocontroller 2570 by connection 2574. Inflation device 2564 is shownconnected to controller 2570 by connection 2576.

In various embodiments, distal end 2524 of catheter 2520 is insertedinto a vessel, for example, the coronary sinus. Once distal end 2524 ofcatheter 2520 is in place, balloon 2547 may be inflated by inflationdevice 2564. Pressure measuring device 2562 measures pressure distal toballoon 2547 through pressure port 2544 on side-wall of shaft 2522. Oncethe pressure waveform in the vessel has become ventricularized, forexample, blood beating against balloon 2547 in a similar rhythm to aheartbeat, inflation of balloon 2547 is stopped by controller 2570. Atthis point, pressure increasing device 2560 begins to force a liquidthrough catheter 2520 to soft tip 2530 to outlet port 2592. Liquid isforced into the vessel distal to balloon 2547. Pressure measuring device2562 measures pressure distal of balloon while liquid is being forced bypressure increasing device 2560. Controller 2570 controls pressureincreasing device 2560 to regulate fluid flow and pressure, by theinformation provided by pressure measuring device 2562. After asufficient period of time, controller 2570 stops the delivery of liquidby pressure increasing device 2560, then deflates balloon 2547 withinflation device 2564, and catheter 2520 may then be removed from thevessel. It is worth explaining that although references are made hereinto a pressure lumen and a pressure-sensing device (e.g., such as isdescribe above with respect to FIG. 25), it is considered that apressure lumen, can be used for measuring other parameters includingflow, oxygen saturation, pH, or temperature. Similarly, apressure-sensing device, can be exchanged with another device to measureone of the parameters above. Moreover, although system 2500 describes acatheter with three lumens, it is envisioned that a cannula or catheter(e.g., such as is describe above with respect to FIG. 25), may have fouror more lumens. Specifically, a cannula or catheter as described herein,may include a balloon inflation lumen, a delivery lumen, and twoparameter measurement lumens (e.g., such as one lumen to measurepressure and another lumen to measure temperature).

Delivery catheter 2620 is shown in FIGS. 26, 27, 28 and 29. Deliverycatheter 2620 includes flexible shaft 2622 having distal end 2624,proximal end 2626 and delivery lumen 2628 extending therebetween. Invarious embodiments, shaft 2622 is at least about 50 cm long, and inanother embodiment, at least about 60 cm long, between proximal end 2626and distal end 2624, so that distal end 2624 may be positioned in thecoronary sinus or another vessel (as seen in FIGS. 33 and 34) withproximal end 2626 extending out of the patient through a puncture in aperipheral vein, such as a femoral vein. Shaft 2622 is made of amaterial such that it is sufficiently flexible to navigate this pathwithout difficulty. In various embodiments, shaft 2622 is made of abiocompatible polymer such as a polyether block amide resin, forexample, PEBAX®, a registered trademark of Atochem, with a durometer ina range of about 50 to about 72 Shore D. In another embodiment, aportion, including the entire portion, of shaft 2622 is radiopaque topermit fluoroscopic observation thereof to facilitate positioning.Radiopaque markers may be applied to the shaft near distal end 2624, ora filler such as barium sulfate may be added to the polymeric materialused to form shaft 2622.

To allow percutaneous introduction of delivery catheter 2620 in aperipheral vein, in various embodiments, shaft 2622 will have an outerdiameter (“OD”) of no more than about 5.0 mm from distal end 2624 to atleast about 30 cm proximal thereto, and in another embodiment, to atleast about 50 cm proximal thereto.

In some embodiments, delivery catheters described herein (e.g., such asballoon catheter 2200, delivery catheter 2520, or delivery catheter2620) may be adapted for introduction through a commercially-available 9French or 10 French introducer sheath or a suitably sized guidecatheter, or by feeding over a guidewire, or for introduction bysurgical cut-down into a comparably-sized blood vessel (e.g., such as anartery of vein, including a peripheral vein). Additionally, the deliverycatheters described herein may be adapted to be introduced through guidecatheters (e.g., such as catheter 302, 502, 2000, or 2100) to bedelivered to a location of a blood vessel from which the distal end ofthe delivery catheter (e.g., such as distal end 2524 or 2624) may beadvanced to a treatment region of a blood vessel to be treated byinfusing a treatment agent (e.g., such as by infusion through system2500, as described above).

In various embodiments, a guide catheter (e.g., such as a guide catheterto be used with a delivery catheters described herein) is adapted to befed into a femoral vein, then to an external iliac vein, then to acommon iliac vein, to inferior vena cava 116), then into right atrium122, and into coronary sinus 3286 (see FIG. 32), and can then be fedfurther into venus system on exterior of heart (see FIGS. 33 and 34). Inanother embodiment, guide catheter is adapted to be fed into an externaljugular vein or an internal jugular vein, into superior vena cava 126,and then into right atrium 122 and into coronary sinus 3286, where guidecatheter may stay in coronary sinus 3286 (see FIG. 32), or be fedfurther into the venus system on exterior of the heart (see FIGS. 33 and34).

In various embodiments, a suitable guide catheter is described in aco-pending patent application Ser. No. 10/293,535, filed on Nov. 12,2002. Co-pending patent application Ser. No. 10/293,535, filed on Nov.12, 2002 is herein incorporated by reference in its entirety. The guidecatheter disclosed in the co-pending patent application may be insertedinto a blood vessel, such as a femoral vein. Note that that guidecatheter has a first convex curved portion, a concave curved portiondistal to the first convex curved portion, and a second convex curvedportion distal to the concave curve portion. Suitable guide cathetersmay also include an occlusion balloon at a distal end (e.g., such ascatheter 302, 502, and 2100 having balloons 308, 510, and 2112,respectively). Other suitable guide catheters include the Viking OpimaLine™ (a trademark of Guidant Corporation), the ACS Viking™ line ofguide catheters (a trademark of Guidant Corporation), and the ACS RADCurve™ line of guide catheters (a trademark of Guidant Corporation).Appropriate guide catheters also include EasyTrak® guiding catheters,Rapido® guiding catheters, and telescoping guide catheters, for example,CS-MP REF 7300 and CS-IC 90 REF 666776-101.

Referring again to FIGS. 26-29, soft tip 2630 (of for example, PEBAX®with a durometer of 20 to 30 Shore D) is bonded to distal end 2624 ofshaft 2622 to reduce the risk of trauma to the coronary sinus or othervessels. Delivery lumen 2628 extends from fitting 2632 at proximal end2626 through shaft 2622 and through soft tip 2630 to outlet port 2692 inthe distal end of soft tip 2630. Side holes 2634 in communication withdelivery lumen 2628 may also be provided near distal end 2624 of shaft2622 as shown in FIG. 27. In various embodiments, delivery lumen 2628preferably has a cross-sectional area no less than about 4 mm² at anypoint between proximal end 2626 and outlet port 2692 to facilitatedelivery of treatment agent at sufficient flow rates while keeping thepressure at which the treatment agent is delivered low enough to avoidexcessive hemolysis if there is a blood component of the treatmentagent, as described more fully below. In various embodiments, the innerdiameter (ID) of delivery lumen 2628 is at least about 2.8 mm, andheight H1 is at least about 1.8 mm.

Catheter 2620 is provided with balloon 2647 on distal end 2624 ofcatheter 2620 which is adapted to occlude the coronary sinus or anothervessel (see FIGS. 33 and 34) when inflated. In various embodiments,balloon 2647 includes a biocompatible polymer such as a polyether blockamide resin, for example, PEBAX® (a registered trademark of ATOCHEMCORPORATION, PUTEAUX, FRANCE). In another embodiment, balloon 2647 is abiocompatible polymer blend of polyurethane and silicone, for examplePurSil™ (a trademark of THE POLYMER TECHNOLOGY GROUP, BERKELEY,CALIFORNIA). In various embodiments, balloon 2647 has an inflateddiameter range of about four mm to about nine mm, an uninflated diameterof about three mm, and a working length of about six mm. For instance, aballoon as described above with respect to balloons 308, 510, and 2112,may be inflated as described below with respect to balloons 8810 and9510, or by an inflation device such as apparatus 9700 or 9800 of FIG.75A-81.

In various embodiments, balloon 2647 may be located at least about 15 mmfrom distal end 2624 of shaft 2622 so that, during positioning, ifballoon 2647 is pulled out of the coronary sinus, there is sufficientlength of shaft 2622 distal to the balloon that will remain in thecoronary sinus to eliminate the need to relocate distal end 2624 in thecoronary sinus.

In various embodiments, balloon 2647 is formed by dipping a mandrel inliquefied polymer and curing as needed. Balloon 2647 may be attached toshaft 2622 by, for example, heat welding or an adhesive.

Inflation lumen 2636 extends through shaft 2622 and is in communicationwith the interior of balloon 2647 through opening 2637. Near proximalend 2626, inflation lumen 2636 is connected to inflation extension tube2638 attached to shaft 2622 having fitting 2640 at its proximal end forattachment to an inflation fluid delivery device. In variousembodiments, inflation lumen 2636 is configured to allow delivery ofinflation fluid or gas at a sufficient rate to fully inflate balloon2647 in about two seconds. In another embodiment, inflation lumen 2636has a height H2 of about 0.5-0.9 mm and a width W of about 0.9-1.3 mm.Inflation lumen 2636 may alternatively be a coaxial lumen around shaft2622, enclosed by a separate tubular member (not shown). Extension tube2638 may have a surrounding material, sleeve, cannula or lumen, such asdescribed below with respect to infusion lumen 9520 or accessory lumen9530 of FIGS. 69A-F.

Optionally, pressure relief valve 2641 may be connected to inflationextension tube 2638 to prevent overinflation of balloon 2647, whichmight damage the tissue of the coronary sinus or another vessel.Pressure relief valve 2641 is configured to open and relieve fluidpressure from inflation lumen 2636 when balloon 2647 exceeds the maximumdesired inflated pressure or diameter, e.g., about 9 mm. This may beaccomplished by pre-inflating balloon 2647 to the maximum inflateddiameter without pressure relief valve 2641 mounted to the deliverycatheter, thereby plastically deforming balloon 2647 to its fullyinflated size. Balloon 2647 is then collapsed onto the shaft by applyinga vacuum to inflation lumen 2636, and pressure relief valve 2641 ismounted to inflation extension tube 2638. In use, when delivery catheter2620 is positioned in the coronary sinus, inflation of balloon 2647 tothe desired inflated size will require relatively low pressure, e.g.less than about 0.5-2.0 psi. However, once the maximum inflated size isreached, the pressure will increase significantly, causing pressurerelief valve 2641 to open, thus preventing overinflation of balloon2647. A suitable pressure relief valve 2641 is available from, forexample, Smart Products, Inc. of San Jose, Calif., under the name “LuerCheck Valve.”

In another embodiment, balloon 2647 may be self-inflating, wherein thetreatment agent itself acts as the inflation fluid for balloon 2647,eliminating the need for a separate inflation lumen 2636 in shaft 2622.In this embodiment, delivery lumen 2628 communicates with the interiorof balloon 2647 in such a way that balloon 2647 will inflate fully toocclude the coronary sinus only during delivery of treatment agent. Forexample, a fluid path between delivery lumen 2628 and balloon 2647 maybe provided such that all or a major portion of the treatment agentdelivered through delivery lumen 2628 first enters the balloon to causeballoon 2647 to inflate, before treatment agent flows into the coronarysinus through outlet holes in shaft 2622 distal to balloon 2647, orthrough outlet holes in the balloon itself. One way to accomplish thisis by a reduction in the diameter of the lumen distal to balloon 2647such that a sufficient head pressure is established to inflate balloon2647 and administer a treatment agent from shaft 2622.

Pressure lumen 2642 may also be provided in shaft 2622 which opens atpressure port 2644 on side-wall of shaft 2622 near distal end 2624, orin soft tip 2630 as illustrated. Pressure lumen 2642 is connected toextension tube 2646 attached (e.g., via adhesive) to shaft 2622 nearproximal end 2626 and includes fitting 2648 at its proximal end suitablefor connection to pressure monitoring equipment. In this way, pressurein the coronary sinus distal to balloon 2647 may be monitored duringtreatment agent delivery to ensure that pressure within the coronarysinus is maintained at a safe level. Extension tube 2646 may have asurrounding material, sleeve, cannula or lumen, such as described belowwith respect to infusion lumen 9520 or accessory lumen 9530 of FIGS.69A-F.

Pressure relief valve (e.g., not shown, but such as relief valve 2641)connected to inflation extension tube 2638, may also be connected todelivery lumen 2628 to ensure that treatment agent pressure does notexceed a predetermined level, avoiding hemolysis in the blood componentof the fluid or protecting the coronary sinus from excessive infusionpressure. In various embodiments, pressure in the range of about zero toabout five mmHg could be measure at port 2644.

As shown in FIG. 29, distal portion of shaft 2622 may include deliverylumen 2628, inflation lumen 2636, pressure lumen 2642, and guidewirelumen 2691. Guidewire lumen 2691 is adapted to receive a guidewire,where the guidewire may be used for navigating through the vasculatureor the guidewire may be provided with a balloon on a distal end of theguidewire.

As shown in FIG. 27, distal portion of shaft 2622 may include first bend2650 and second bend 2652, which facilitate the placement of distal end2624 in the coronary sinus. In various embodiments, second bend 2652 maybe distance L2 of between about three mm and 10 mm in distance fromdistal end of soft tip 2630, and first bend 2650 may be a distance L₁ ofbetween 20 mm and 40 mm in distance proximal to second bend 2652. Firstand second bends 2650, 2652 may subtend various angles depending uponpatient anatomy and surgeon preference. In various embodimentsconfiguration, first bend 2650 subtends an angle A of between about 20°and about 70° relative to the longitudinal axis of proximal portion 2654of shaft 2622. In another embodiment, second bend 2652 may subtend anangle B of about 30° to about 40° relative to mid-portion 2656 of shaft2622.

A liquid containing a treatment agent or drug, e.g., a caroporidesolution, may be introduced into proximal end 2626 of catheter 2620,which extends outside of the patient, under sufficient pressure so thatthe fluid containing the treatment agent can be forced to pass throughthe coronary sinus, through the capillary beds (not shown) in thepatient's myocardium, and optionally through coronary arteries (notshown) and ostia associated with the respective coronary arteries (notshown) into the ascending aorta (not shown).

In various embodiments, balloon 2647 on the distal extremity of catheter2620 is inflated to occlude the coronary sinus or another vessel toprevent fluid loss into the right atrium. A liquid containing atreatment agent such as adenosine is directed through catheter 2620 intothe coronary sinus or another vessel and the pressure and volumetricflow rate of the treatment agent within the coronary sinus or anothervessel are maintained sufficiently high (e.g. at least 100 ml/min atabout 40 mm Hg) so that the treatment agent will pass through thecoronary veins, and reaching the capillary beds, and optionally on tothe coronary arteries (not shown) and out the ostia (not shown).

Treatment agent is delivered through delivery catheter 2620 at a flowrate sufficient to maintain desired treatment by periodic or continualinfusions. However, treatment solution pressure within the coronarysinus or another vessel should be less than about 50 mm Hg to avoidtissue damage. In various embodiments, the treatment agent is a mixtureof blood and a treatment agent such as an antioxidant, in variousembodiments at a ratio or four parts blood to one part antioxidantsolution (by volume). This antioxidant solution may be mixed intooxygenated blood.

The treatment agent may be directed to fitting 2632 on proximal end ofdelivery catheter 2620, and delivered to the coronary sinus, or anothervessel, in various embodiments at a flow rate of at least about 100ml/min. and in another embodiment, at about 200 ml/min. If treatmentagent includes a blood component, the pressure required to pump thetreatment agent through the lumen of the delivery catheter (“pumppressure”) should not exceed 300 mmHg to avoid excessive hemolysis ofthe blood component. Treatment agent flow through delivery catheter 2620is maintained on a periodic basis, e.g., about every 15-30 seconds for2-4 minutes, so long as the heart is to remain under treatment.

Referring now to FIG. 30, another embodiment of a catheter system isillustrated. Catheter system 3000 includes delivery catheter 3020 (forexample, delivery catheter 2620, 3122, 3201, 3510, 3920, or any othercatheter or cannula.). Delivery catheter 3020 includes proximal ends3026 (for example, 2626) and distal end 3024 (for example, 2624, 3112,3260). Delivery catheter 3020 includes a delivery lumen (not shown) (forexample, 2628, or any other delivery lumen, tube or cannula as describedherein). Delivery lumen connects outlet port 3092 (for example, 2692,3162, 3154, 2628, 3228, 3992, or any other treatment agent delivery orinfusion opening, exit, or port) on distal end 3024 of catheter and hasfitting 3032 (for example, 2632) on proximal end 3026 of catheter.Fitting 3032 may be connected to a pressure increasing device 3050 (forexample, 5600, 5700, or 5800) by device outlet 3004 (for example, 5604,5718, or 5818). Intermediate to device outlet 3004 and fitting 3032there may be located one or more (in series) of pressure-transferringdevice, pressure-maintaining, or pressure-dampening device 3052 (forexample, 5900, 6000, 6100).

On distal end 3024 of catheter is located balloon 3047 (for exampleballoon 8810, 9510, filter device 710, or any other balloon, occlusiondevice, or filter device as described herein) with inflation lumen (notshown) (for example, 2636, 3936, or any other inflation lumen, tube orcannula), where inflation lumen has opening 3037 (for example, 2637,3172), which serves to inflate or deflate balloon 3047. Inflation lumenis through catheter 3020 from opening 3037 (for example, 2637, 3172) toinflation extension tube 3038 (for example, 2638), which has fitting3040 (for example, 2640) at the proximal end of inflation extension tube3038. There is also optionally provided pressure relief valve 3041 (forexample, 2641) adjacent to fitting 3040. Inflation device 3070 (forexample, apparatus 9700, 9800 of FIGS. 75A-81 or any other balloon orocclusion device inflation device) may be connected to fitting 3040.Extension tube 3038 may have a surrounding material, sleeve, cannula orlumen, such as described below with respect to infusion lumen 9520 oraccessory lumen 9530 of FIGS. 69A-F.

Delivery catheter 3020 may also have a pressure lumen (not shown) (forexample, 2642, 3142, 3220, accessory lumen 9530, or any other lumen,tube, or cannula capable of measuring pressure or inserting a pressuresensing device through), where pressure lumen has pressure port 3044(for example, 2644, 3136, 3228, 3944) at distal end of pressure lumen.Pressure lumen extends from pressure port 3044 to extension tube 3046(for example, 2646). Extension tube 3046 has fitting 3048 (for example,2648) at proximal end of extension tube 3046. Pressure-sensing device3060 may be connected to fitting 3048. Extension tube 3046 may have asurrounding material, sleeve, cannula or lumen, such as described belowwith respect to infusion lumen 9520 or accessory lumen 9530 of FIGS.69A-F.

In various embodiments, system 3000 has controller 3080, such as acontroller (e.g., including an automatic, computer, or machinecontroller) adapted to control a pressure increasing device, apressure-sensing device, or an inflation device as described herein.More particularly, pressure-sensing device 3060 may be connected topressure measurement connection 3008 (for example, 5708 or 5808 of FIGS.57 and 58) of pressure increasing device 3050 by pressure measurementconnection 3062. Optionally, there may be provided system controller3080, for example, a computer or mini-computer, which is connected topressure increasing device 3050, pressure-sensing device 3060, orinflation device 3070. For example, system controller 3080 may access amemory including instructions (e.g., such as machine readableinstructions) to control a pressure increasing device, apressure-sensing device, an inflation device, in infusion device, or anydevice or apparatus. Specifically, controller 3080 may be used tocontrol inflation or deflation of a balloon to various outer diameters(e.g., see FIGS. 55 and 68 herein, which illustrates a balloon outsidediameter growth rate) by inflating a balloon with a selected inflationpressure or volume.

Moreover, system controller 3080 may be used to control an amount oftreatment agent infused, a period of time during which treatment agentis infused, a period of time during which an occlusion device occludes ablood vessel (e.g., such as first period of time 9670, or a period oftime that filter device 720 (e.g., see FIGS. 7-19 and accompanying text)is expanded within the blood vessel), or a period of time during whichblood or treatment agent is allowed to perfuse or flow through atreatment region in a blood vessel (e.g., such as second period of time9680). Similarly, system controller 3080 may be used to control atreatment process for infusion of a treatment agent into an artery orvein of a patient using devices, apparatus, methods, or processesdescribed herein (e.g., such as according to the process described withrespect to FIG. 3, 19, 54, 55, 63, or 82).

A suitable self-inflating balloon configuration is illustrated in FIG.31. FIG. 31 illustrates the structure and operation of self inflatingballoon 3147 and flow tip 3148 of catheter 3120. Pear shaped balloon3147 tapers gradually from its widest diameter to form distal circularcuff 3168, and tapers more quickly from its widest diameter to formproximal circular cuff 3170. Proximal cuff 3170 coaxially receivescatheter body 3122 and is attached thereto to form a fluid tight sealbetween cuff 3170 and catheter body 3122. Distal cuff 3168 coaxiallyreceives and attaches to flow tip 3148.

Plurality of radial holes 3172 extend through body of catheter 3122 fromwithin infusion lumen 3128, proximal of flow tip base plug 3152, intointerior space 3174 enclosed by balloon 3147. Thus the flow of treatmentagent through catheter 3120 shown by arrows 3190 exits infusion lumen3128 through holes 3172, enters balloon interior 3174, flows into flowchannels 3158 and exits each flow channel 3158 through its side exits3162, or distal exits 3154. The aggregate cross sectional area of holes3172 filling balloon interior 3174 exceeds the aggregate cross sectionalarea of flow channels 3158 draining balloon interior 3174, providing apositive pressure within balloon interior 3174 to keep balloon 3147inflated while the treatment agent flows through catheter 3120.

Pressure monitoring lumen 3142 extends through one of open channels 3158via extension tube 3175. Extension tube 3175 may have a surroundingmaterial, sleeve, cannula or lumen, such as described below with respectto infusion lumen 9520 or accessory lumen 9530 of FIGS. 69A-F. Extensiontube 3175 extends from flow tip body 3150, where pressure monitoringlumen 3142 exits flow tip body 3150, through one of flow channels 3158,and terminates proximally adjacent flow channel distal exit (not shown),to form pressure lumen distal opening 3136. The pressure monitoringequipment (not shown) is thus in pressure communication with the insideof the coronary sinus or another vessel in which pressure lumen distalopening 3136 is located. Because the pressure lumen distal opening 3136is recessed into the flow channel 3158, there is less chance of itbecoming occluded by the wall of the coronary sinus, or another vessel.

Also note that stylet well 3176 can coaxially sink into base plug 3152of flow tip 3148 for receiving a stylet (not shown), and providingadditional reinforcement at distal end 3156 of catheter body 3122 wherethe stylet (not shown) impacts base plug 3152 of flow tip 3148.

FIG. 32 depicts catheter 3201 positioned within heart 100. Catheter 3201may be inserted percutaneously through a blood vessel, such as an arteryor vein. Specifically, catheter 3201 can be advanced through apercutaneous venus entry, such as through a femoral vein, and tip 3212is guided through right atrium 122 into coronary sinus 3286. Blooddrains into right atrium 122 via superior vena cava 126 and interiorvena cava 116, and from coronary sinus 3286 via coronary sinus ostium3288. Moreover, blood drains from the myocardium to coronary sinus 3286via great cardiac vein 3290 and small cardiac vein 3292.

Tip 3212 having port 3214 is inserted into coronary sinus 3286 to adepth from about zero to about four inches (zero to about 10.2 cm) fromcoronary sinus ostium 3288. Optionally, markers 3218 may be provided oncatheter 3201 and optionally spaced about two inches apart alongcatheter 3201; in various embodiments, markers 3218 are radiopaque.

Referring now to FIG. 33, which illustrates diaphragmatic surface ofheart 3300. Coronary sinus 3286 is shown feeding into right atrium.Great cardiac (anterior interventricular) vein 3290, oblique vein ofleft atrium 3310, and posterior vein of left ventricle 3304 feed intocoronary sinus 3286. Also, middle cardiac (posterior interventricular)vein 3306, and small cardiac vein 3308 feed into coronary sinus 3286.All the veins are provided with arrows to show direction of ordinaryblood flow into coronary sinus 3286 and into right atrium.

Referring now to FIG. 34, sternocostal surface of heart 3301 is shown.Great cardiac (anterior interventricular) vein 3290 is shown, as areanterior cardiac veins of right ventricle 3314, and small cardiac vein3308.

Left coronary artery 3320 and right coronary artery 3322 feed out ofaorta 3350. Branching off of left coronary artery 3320 are circumflexbranch of left coronary artery 3324, and anterior interventricularbranch (left anterior descending) of left coronary artery 3344, andinterventricular septal branches 3326. Feeding off of right coronaryartery 3322 are atrial branch of right coronary artery 3330, and rightmarginal branch of right coronary artery 3328.

Referring again to FIG. 33, right coronary artery 3322 is shown. Feedingoff of right coronary artery 3322 are right marginal branch 3338, andinterventricular septal branches 3342. Other branches from left coronaryartery (3320 in FIG. 34) are circumflex branch of left coronary artery3324, and posterior left ventricular branch 3340. Also shown in FIG. 33are sinuatrial nodal branch 3332, and sinuatrial node 3334.

FIG. 35 illustrates distal end 3560 of catheter 3510 within coronarysinus 3286. Catheter 3510 has tip 3514 at distal end 3560, and pluralityof lumen outlets 3528 proximal to tip 3514. Balloon 3522 is shownoccluding coronary sinus 3286 and coronary sinus ostium 3288 adjacent toright atrium wall 3556. Balloon 3522 on catheter 3510 may also be usedto occlude other veins distal to coronary sinus 3286, for example, greatcardiac vein 3290, anterior cardiac vein of right ventricle 3314, andsmall cardiac vein 3308 (shown in FIGS. 33 and 34). In this embodiment,a self-inflating balloon is shown with infusion lumen 3518 through whicha treatment agent flows and inflates balloon 3522 then flows out oflumen outlets 3528. Pressure-sensing lumen 3520 is also provided. Inanother embodiment, a third lumen was provided (not shown) to inflateballoon 3522 when balloon 3522 is not self-inflating. There is alsoprovided guidewire 3570, having distal end 3576. Guidewire 3570 is fedthrough guidewire lumen 3572, which guidewire lumen 3572 has distalopening 3574 at tip 3514.

Referring now to FIG. 36 is a staggered tip of a balloon catheter.Balloon catheter 3600 has distal end 3602 and proximal end (not shown).Adjacent distal end 3602 of catheter is balloon 3604. Balloon inflationlumen 3606 has distal end and opening 3608 within balloon 3604 toinflate or deflate balloon 3604. Pressure-sensing lumen 3610 has distalend and opening 3612 which enables pressure-sensing lumen 3610 to sensepressure or other measurements or parameters wherever distal end 3602 ofcatheter is placed. Delivery lumen 3614 has distal end and opening 3616which enables a fluid path from proximal end (not shown) of catheter todistal end 3602 of catheter.

Staggered tip of catheter 3600 may enable easier tracking of distal end3602 of catheter through a blood vessel. In various embodiments,pressure-sensing lumen 3610 or catheter body 3620 adjacentpressure-sensing lumen 3610 have tapered cut 3622 which may be curved.According to some embodiments, tapered cut 3622, may have an angle and atapered shape, such as is described above with respect to tapered cut2222 of FIG. 22. In various embodiments, distance L₁ marked withreference numeral 3624 is the distance between distal end 3612 ofpressure-sensing lumen 3610 and distal end 3616 of delivery lumen 3614.In various embodiments, L₁ 3624 may be between about 0.5 millimeters andfive millimeters.

In another embodiment, catheter 3600 is illustrated. Catheter hasballoon inflation lumen 3606, balloon 3604, delivery lumen 3610 havingopening 3612, and pressure-sensing lumen 3614 having opening 3616.Catheter 3600 has a staggered tip where opening 3612 of delivery lumen3610 is distance L₁ 3624 from opening 3616 of pressure-sensing lumen3614. In addition, catheter body 3620 adjacent opening 3612 of deliverylumen 3610 may have a tapered or curved shape 3622.

In another embodiment, catheter 3600 may include marker 3630, forexample a radio-opaque marker, which may serve to ease visualization ofdistal end 3602 of catheter 3600 with a diagnostic or visualizationsystem.

Referring now to FIG. 37, is a staggered tip of a balloon catheter.Balloon catheter 3700 has distal end 3702 and proximal end (not shown).Adjacent distal end 3702 of catheter is balloon 3704. Balloon inflationlumen 3706 has distal end and opening 3708 within balloon 3704 toinflate or deflate balloon 3704. Pressure-sensing lumen 3710 has distalend and opening 3712 which enables pressure-sensing lumen 3710 to sensepressure or other measurements or parameters wherever distal end 3702 ofcatheter is placed. Delivery lumen 3714 has distal end and opening 3716which enables a fluid path from proximal end (not shown) of catheter todistal end 3702 of catheter. Staggered tip of catheter 3700 may enableeasier tracking of distal end 3702 of catheter through a blood vessel.In various embodiments, pressure-sensing lumen 3710 or catheter body3720 adjacent pressure-sensing lumen 3710 have tapered cut 3722 whichmay be curved. According to some embodiments, tapered cut 3722, may havean angle and a tapered shape, such as is described above with respect totapered cut 2222 of FIG. 22. There is also provided an indentation 3740proximal to distal end 3702, with guidewire lumen 3742 distal toindentation 3740. Indentation 3740 and guidewire lumen 3742 are adaptedto receive guidewire 3744. Guidewire 3744 has proximal end (not shown)and distal end 3746. Guidewire 3744 may be provided with balloon 3748adjacent distal end 3746. In use, catheter 3700 may be tracked over theguidewire through by feeding distal end 3702 of catheter over guidewire3744 by way of lumen 3742. This “over the wire” (OTW) is also known asmonorail.

Referring now to FIG. 38, the staggered tip of a balloon catheter.Balloon catheter 3800 has distal end 3802 and proximal end (not shown).Adjacent distal end 3802 of catheter is balloon 3804. Balloon inflationlumen 3806 has distal end and opening 3808 within balloon 3804 toinflate or deflate balloon 3804. Pressure-sensing lumen 3810 has distalend and opening 3812 which enables pressure-sensing lumen 3810 to sensepressure or other measurements or parameters wherever distal end 3802 ofcatheter is placed. Delivery lumen 3814 has distal end and opening 3816which enables a fluid path from proximal end (not shown) of catheter todistal end 3802 of catheter.

Staggered tip of catheter 3800 may enable easier tracking of distal end3802 of catheter through a blood vessel. In various embodiments,pressure-sensing lumen 3810 or catheter body 3820 adjacentpressure-sensing lumen have tapered cut 3822 which may be curved.According to some embodiments, tapered cut 3822, may have an angle and atapered shape, such as is described above with respect to tapered cut2222 of FIG. 22. In various embodiments, distance L₁ marked withreference numeral 3824 is the distance between distal end 3812 ofpressure-sensing lumen 3810 and distal end 3816 of delivery lumen 3814.In various embodiments, L₁ 3824 may be between about 0.5 mm and aboutfive mm.

Catheter 3800 may also include marker 3830, for example, a radio-opaquemarker, which may serve to ease visualization of distal end 3802 ofcatheter 3800 with a diagnostic visualization system.

Catheter 3800 may also include guidewire lumen 3842 through catheter3800. Guidewire lumen 3842 has distal end and opening 3843 adjacentdistal end 3802 of catheter. Guidewire lumen 3842 is adapted to receivea guidewire. Guidewire 3844 is illustrated, where guidewire 3844 hasdistal end 3846 and balloon 3848 adjacent distal end 3846.

Referring now to FIG. 39, which shows catheter 3920 within blood vessel3910 (e.g., such as a vein or artery). Catheter 3920 includes balloon3947 on distal end 3924 of catheter 3920. Also, on distal end 3924 isoutlet port 3992 to deliver a treatment agent into blood vessel 3910.Pressure port 3944 is on distal end 3924 to measure a pressure in bloodvessel 3910. Balloon 3947 is inflated by outlet ports of inflation lumen3936. Blood vessel 3910 is divided into two portions, first portion 3914is distal to balloon 3947, and second portion 3912 is proximal toballoon 3947. Balloon 3947 serves to seal against inner wall of bloodvessel 3910, and provide a pressure separation between first portion3914 and second portion 3912. In various embodiments, treatment agentflowing through outlet port 3992 serves to increase the size of firstportion 3914 due to the high pressure exerted by treatment agent onblood vessel walls in first portion 3914. This causes first portion 3914to have a larger diameter than second portion 3912, and a frusto-conicalshape taper is created between first portion 3914 and second portion3912. In this embodiment, balloon 3947 is tapered to accommodate thefrusto-conical shape of the taper between first portion 3914 and secondportion 3912.

In various embodiments, balloon 3947 may be tapered by having distal end3949 of balloon have a thinner wall thickness than proximal end 3951 ofballoon 3947, so that fluid or gas inserted into balloon 3947 throughoutlet port of inflation lumen 3936 serves to make the distal end 3949of balloon larger than proximal end 3951 of balloon 3947. In anotherembodiment, balloon 3947 may have uniform wall thickness of proximal end3951 and distal end 3949, but the balloon is molded or formed in atapered shape, or otherwise formed so that balloon 3947 will assume atapered shape when inflated.

In various embodiments, a pressure-sensing device may be connected topressure port 3944 via an attachment to fitting 3648 at proximal end ofextension tube 2646 of catheter 2620 (shown in FIGS. 26-29). In variousembodiments, pressure-sensing device may be attached to proximal end ofpressure lumen 2642 (shown in FIG. 28-29). In another embodiment, apressure-sensing device may be fed through pressure lumen 2642 adjacentto pressure port 2644 on side-wall of shaft 2622 near distal end 2624 ofcatheter 2620 (shown in FIGS. 26-29). In various embodiments,pressure-sensing device is disposable. In another embodiment,pressure-sensing device is a disposable piezo-electric pressure sensor,for example, a piezo-electric pressure sensor manufactured by UtahMedical Products, Inc., which is attached to fitting 2648 (shown in FIG.26).

In various embodiments, an inflation device may be connected toinflation lumen 3936 via attachment to fitting 2640 at proximal end ofinflation extension tube 2638 attached to shaft 2622 and inflation lumen2636 extending through catheter 2620. In various embodiments, theinflation device is a syringe. In another embodiment, the inflationdevice is a pump, for example, a centrifugal pump, a gear pump, or areciprocating pump. In another embodiment, balloon 2647 is inflated withcarbon dioxide, saline, or contrast medium by the inflation device.

Referring now to FIG. 40, is illustrated guidewire 4000. Guidewire 4000has distal end 4002. At distal end 4002 is balloon 4004. Balloon 4004may be inflated or deflated by balloon inflation lumen 4006 thoughguidewire 4000. Balloon inflation lumen 4006 has distal end and opening4008 within balloon 4004. There may be provided one or more markers 4010to aid visualization, for example under fluoroscopy, at distal end 4002of guidewire. Spring 4012 is provided about guidewire at distal end 4002to improve tracking of distal end 4002 through curves. In variousembodiments, spring 4012 imparts a natural curve to distal end 4002. Tip4014 is provided to minimize damage to vessels as tip 4014 travelsthrough vessels. Tip 4014 has diameter L₁ 4016. In various embodiments,L₁ is between about 0.005 inches and 0.025 inches.

Referring now to FIG. 41, guidewire 4100 has proximal end 4101 anddistal end 4102. For ease of illustration, break 4103 is provided.Guidewire has sheath 4106 (e.g., such as sheath 790 as shown anddescribed with respect to FIGS. 7-9) about guidewire from proximal end4101 to distal end 4102. FIG. 41 shows sheath 4106 enclosing occlusiondevice 4108. Distal end 4102 also includes floppy tip 4104. FIG. 42Aillustrates the guidewire of FIG. 41 with the occlusion device open. Asshown in FIG. 42A, sheath 4106 has been laterally moved in the directionof arrows 4110 to uncover occlusion device 4108. Distal end 4102 ofguidewire is within vessel 4112. Vessel 4112 has fluid flow in thedirection of arrow 4113. When sheath 4106 is moved, to uncover occlusiondevice 4108, fluid flow within vessel 4112 forces open occlusion device4108 in the direction of arrows 4109. Occlusion device 4108 thenoccludes vessel 4112 (e.g., such as by since occlusion device beingforced against vessel wall by fluid flow within vessel 4112). Suitablematerials for occlusion device 4108 may include one or more of asynthetic or natural latex or rubber, such as a polymer material; apolyetheramide; a plasticiser free thermoplastic elastomer; athermoplastic blend; a block copolymer of polyether and polyester (e.g.,such as a polyester sold under the trademark Hytrel® of DUPONT COMPANY);a bio-compatible polymer such as a polyether block amide resin (e.g.,for instance, PEBAX® of ATOCHEM CORPORATION); a polycarbonate oracrylonitrile bubadiene styrene (ABS); a biocompatible polymer such as apolyether block amide resin; a styrene isoprene styrene (SIS), a styrenebutadiene styrene (SBS), a styrene ethylene butylene styrene (SEBS), apolyetherurethane, an ethyl propylene, an ethylene vinyl acetate (EVA),an ethylene methacrylic acid, an ethylene methyl acrylate, an ethylenemethyl acrylate acrylic acid, a material from a material family of oneof styrenic block copolymers and polyurethanes, a melt processiblepolymer, urethane, polyurethane, polyethylene, polypropylene,polybutylene, copolymers of ethylene, propylene, butylene, a lowdurometer material, nylon, and other materials that can block fluidflow.

FIG. 42B, is a front view of FIG. 42A from perspective “A”. FIG. 42Bshows an embodiment of occlusion device 4108 having overlappingleaflets. First leaflet 4120 is shown overlapping second leaflet 4122from the front. FIG. 42C, is a side of the occlusion device of FIG. 42Ashowing the occlusion device overlapping leaflets. FIG. 42C showsocclusion device 4108 with second leaflet 4120 overlapping first leaflet4122 from the back. In another embodiment, occlusion device 4208 is asingle member, without leaflets. For instance, occlusion device 4108 maybe a single member with fold lines to prevent crimping of occlusiondevice 4108 when retracted by sheath 4106 (e.g., such as if filterdevice 720 were a solid member or material).

In use, distal end 4102 of guidewire 4100 is fed into vessel 4112. Oncedistal end 4102 of guidewire has been located in the correct position,sheath 4106 may be pulled back in the direction of arrows 4110 to exposeocclusion device 4108. Fluid flow in the direction of arrow 4113, withinvessel 4112, forces open occlusion device 4108 in the direction ofarrows 4109 to occlude vessel 4112. At the end of the procedure, sheath4106 may be advanced in the direction of arrows 4111 to recover ordisengage occlusion device 4108 and force it closed. At that point,distal end 4102 may be removed from vessel 4112. In another embodiment,before removing distal end 4102, sheath 4106 may be removed, and asecond sheath (not shown) may be fed over proximal end 4101 of guidewireto recover occlusion device 4108. Second sheath may have a largerdiameter to trap fluid, particles, or foreign objects which were caughtin occlusion device 4108. In this embodiment, second sheath (not shown)is fed in direction of arrows 4111 until occlusion device 4108 has beenclosed and then distal end 4102 may be removed from vessel 4112.

In various embodiments, occlusion device 4108 may be provided withleaflets or fold lines to ease deployment and recapture of occlusiondevice. For instance, in various embodiments, occlusion device 4108 maybe opened (such as after sheath 4106 has been pulled back) by rotationof guidewire 4100 to cause occlusion device 4108 to rotate in direction4182 to open occlude vessel 4112 (see FIGS. 42A-42C). Specifically,rotation of occlusion device 4108 in direction 4182 causes leaflets ofthe device (e.g., including first and second leaflets 4120 and 4122) toopen. Similarly, occlusion device 4108 may be closed, such as forremoval, by rotation of guidewire 4100 to cause occlusion device 4108 torotate in direction 4184 to recover or disengage occlusion device 4108by forcing it closed (see FIGS. 42B-42C). Thus, rotation of occlusiondevice 4108 in direction 4184 causes leaflets of the device (e.g.,including first and second leaflets 4120 and 4122) to close or form asmaller outer diameter than shown in FIG. 42A.

Referring now to FIG. 43, guidewire 4300 is illustrated having aproximal section 4301 and distal end 4302. Occlusion device 4304 isprovided adjacent distal end 4302. Occlusion device 4304 has a frame4306, and basket 4308 stretched between the structure of frame 4306. Forinstance, frame 4306 is shown having distal frame 4362 and proximalframe 4364 to support basket 4308, such as where basket 4308 forms ascoup, cone, “parachute”, or net shape between distal frame 4362 andproximal frame 4364 by being on, over, between, or attached to distalframe 4362 and proximal frame 4364. Suitable materials for basket 4308include urethane, polyurethane, polyethylene, polypropylene,polybutylene, copolymers of ethylene, propylene, or butylene, latex,elastomers, PEBAX®, nylon and other materials that can block fluid flow.Also, suitable materials for frame 4306 include an elastic material,nitinol (NiTi), or self-expanding materials (e.g., such as shape memoryalloys, including for example, Nickel-Titanium) or other materials thathave shape memory where the memorized shape is the expanded shape. Tomodify the shape (e.g., to restrict the shape) a sheath may be placedover occlusion device 4304. Removing the restriction will allow theshape memory material to return to its memorized shape (e.g., anexpanded shape) without being damaged. In the case shown by FIG. 43,sheath 4310 is provided over guidewire 4300 to be place over or restrainocclusion device 4304 (e.g., sheath 4310 may be a material or functionas described above for sheath 790 or 4106 as described above withrespect to FIGS. 7-9, and 41 respectively).

According to some embodiments, basket 4308 may be connected or attachedto a frame 4306, such as by laser bonding, adhesive bonding, thermalbonding, mechanical restriction (e.g., such as if material basket 4308is woven or sewn through structure of the frame, such as structureincluding gaps between the structure or holes in the frame), and orvarious other appropriate attachment methods as described herein.Likewise, an inner diameter of the frame 4306, such as in inner diameterof proximal frame 4364, may be attached to an outer surface of guidewire4300, such as by laser bonding, adhesive bonding, thermal bonding,mechanical bonding.

In use, distal end 4302 is placed within vessel 4312, with sheath 4310covering occlusion device 4304. When distal end 4302 is located in anappropriate location, sheath 4310 is pulled back, and frame 4306, whichincludes an elastic or expanding material to apply an expanding force toocclusion device 4304, forces open occlusion device 4304 stretchingbasket 4308 across vessel 4312 to occlude fluid flow. In addition, fluidflow in the direction of arrow 4314 forces open occlusion device 4304and acts to press basket 4308 against the walls of vessel 4312, by alsoapplying a force on the inside surfaces of basket 4308 which creates anexpanding force to occlusion device 4304.

According to some embodiments, occlusion devices may include varioustypes of balloons made of various materials and according to variousmanufacturing techniques. For example, in various embodiments, devices720, 2006, 2104, 4108, 4304 as described herein; balloons 308, 314, 510,2112, 2204, 2250, 2547, 2647, 3047, 3147, 3522, 3604, 3704, 3804, 3947,4004, 4420, 4520, 4820, 8810, 9510 as described herein; or any othercatheter, cannula, tube, sheath, balloon or occlusion device, may bemade from or include a polymer material, such as a synthetic or naturallatex or rubber. Moreover, the polymer material may be a polyether blockamide resin, a polyetheramide, or a plasticiser free thermoplasticelastomer, for example, PEBAX®, a registered trademark of Atochem.Similarly, balloons or occlusion devices described herein may be madefrom or include a blend of different types of PEBAX®. In variousembodiments, balloons or occlusion devices described herein may be madefrom or include a styrenic block copolymer (SBC), or a blend of SBC's.Suitable SBC's include SBC's sold under the tradename Kraton Polymers® aregistered trademark of Shell Oil Company, SBC's sold under thetradename Vector® a registered trademark of Dexco Polymers, and SBC'ssold under the tradename Europrene® a registered trademark of PolymeriEuropa.

In fact, in some embodiments, balloons mentioned above, or otherballoons or occlusion device, may include various types of ahigh-compliance or low-tension balloons, such as a composite ormulti-layer expanded PolyTetraFlouroEthylene (ePTFE) balloon having aninner liner. For example, FIG. 44 is a cross-sectional view of a cannulaand a balloon. As shown in FIG. 44, cannula 4410 (e.g., such as acannula having a dimension suitable for percutaneous advancement througha blood vessel, such as advancement in direction 4586 through bloodvessel 4490) includes proximal end 4412, distal end 4414, and exteriorsurface 4416. FIG. 44 also shows balloon 4420 (e.g., such as balloonmentioned above, or another balloon or occlusion device) axiallyconnected to exterior surface 4416 of cannula 4410, at or adjacentdistal end 4414. Also shown are diameter of cannula DC, pre-inflationdiameter of balloon DM, inflated diameter of balloon D2, post-inflationdeflated diameter of balloon DP, and diameter of vessel DV.

According to some embodiments, balloon 4420 may have a property suchthat when inflated balloon 4420 will expand in size to an outer diametersufficient for occlusion of a blood vessel at an inflation pressure (orat an inflation volume with respect to balloon 8810 or apparatus 9700 or9800 of FIGS. 75A-81) and less than sufficient to cause an axial forceon an inner diameter of the blood vessel. For instance, FIG. 44 showsballoon 4420 inflated to outer diameter D2 sufficient for occlusion ofblood vessel 4490 at inflation pressure PR, which is a pressure lessthan sufficient to cause an axial force, such as a force in directions4487, on inner diameter 4492 of blood vessel 4490.

More particularly, balloon 4420 may include a property such that wheninflated to volume V1, balloon 4420 will expand in size to outerdiameter D2 that is approximately inner diameter DV of blood vessel 4490at inflation pressure PR, which is a pressure less than sufficient toexert an axial strain on blood vessel 4490 in directions 4487. Thus,balloon 4420 may be a high-compliance balloon that expands radially andlongitudinally upon inflation and forms a plurality of radial outerdiameters during inflation to an outer diameter sufficient to occludethe blood vessel at an inflation pressure that does not appreciablyexpand the blood vessel radially (e.g., such as by occluding the bloodvessel at a location while the inner diameter of the blood vessel at thelocation stays within five percent its pre-occlusion inner diameter).Furthermore, balloon 4420 may be a low-tension balloon, such as aballoon that expands radially and longitudinally upon inflation andforms a plurality of radial outer diameters during inflation anddeflation, but does not form wings. For example, balloon 4420 may have aballoon pre-inflated outer diameter DM between three mm and five mm atan inflation pressure of between zero atmospheres and one atmosphere inpressure, and a balloon inflated outer diameter D2 between five mm andnine mm at an inflation pressure between six atmospheres and eightatmospheres in pressure. In addition, according to some embodiments,pressure PR may be a pressure sufficient to cause balloon 4520 toocclude the blood vessel without radially expanding the blood vessel.

In addition, balloon may have a property to cause post-inflationdeflated outer diameter DP of balloon 4420 to retract to within 20% ofpre-inflated outer diameter DM of balloon 4420. It is also contemplatedthat balloon 4420 may include one or more of the followingcharacteristics: effective modulus of less than 1.5 MPa (e.g., such asduring insertion into a blood vessel, use as an occlusion device, andremoval from the blood vessel), and elongation of less than 500% atbreaking, a tension set of less than 30%, a tension strength of at least200 MPa, and an inflation range of pressure between zero and sixatmospheres in pressure. In various embodiments, balloon 4420 may have atension set of less than 30% in residual strength after elongation to300%, such as by having a tension set of 20%, 15%, 10%, or 5%.Specifically, according to various embodiments, balloon 4420 may have aproperty to withstand an inflation pressure of between six and eightatmospheres of pressure and retract to within 20% of balloon 4420'sinitial pre-inflation dimension, upon removal of inflation pressure.

It is also contemplated that balloon 4420 may have a wall thickness thatvaries with respect to the axis of cannula 4410, so that when balloon4420 is inflated, it has a tapered profile. For instance, according tovarious embodiments, balloon 4420 has a first wall thickness at firstaxial distance 4432 from distal end 4414 of the cannula and a differentsecond wall thickness at different second axial distance 4434 fromdistal end 4414 of cannula 4410. Thus, when balloon 4420 is inflated, itwill expand to a first outer diameter at distance 4432 and a differentsecond outer diameter at distance 4434.

Similarly, it is contemplated that balloon 4420 may have a pre-inflatedouter diameter that varies along the axis of cannula 4410 so that whenballoon 4420 is inflated, it has a tapered profile. In variousembodiments, when deflated, balloon 4420 has a first pre-inflated outerdiameter at distance 4432 and a second pre-inflated outer diameter atdistance 4434. Thus, when inflated, balloon 4420 will expand in size toa first outer diameter at distance 4432 and a different second outerdiameter at distance 4434. An illustration of a balloon having a taperedprofile is shown in FIG. 39.

In accordance with embodiments, balloon 4420 may be formed by variousappropriate processes. For example, balloon 4420 may be formed byinjection molding a material, extruding a material, solvent casting amaterial, or dip coating a material to form a balloon. Moreover, it iscontemplating that extruding may include extruding a material such thatballoon 4420 has a deflated outer diameter in a range of between 0.5 mmand five mm in diameter. For instance, material may be extruded suchthat balloon 4420 has a deflated outer diameter of 1.5 mm, and athickness sufficient to reach an inflated outer diameter of nine mm atless than six atmospheres of inflation pressure.

Furthermore, in embodiments, balloon 4420 may include one or more of asilicone rubber; a polyurethane such as Pursil™, or anotherbiocompatible silicone polyether urethane; Pebax™ such aspolyether-block co-polyamide polymer, polyether-block anide; dienepolymers and their copolymers; isoprenes; neoprenes; diene; styrene;butadienes; styrene-isoprene-styrene block co-polymers;styrene-butadiene-styrene co-polymers; partially or fully crosslinkedversions of these same polymers, such as a Kraton™ (e.g., such asKraton™ 1161K, which is a styrene-isoprene-styrene tri-block co-polymerwith 85% isoprene and 15% styrene), any styrene-isoprene-styrenetri-block co-polymer with up to 100% isoprene and up to 50% styrene;unsaturated dienes, their co-polymers and partially or fully crosslinkedversions of these same; and an aliphatic polymethane with polydimethylsiloxane backbone. Note that for bondability of such polymers, one ormore functional groups may be chemically added to the polymer structure.In particular, balloon 4420 may include one or more of a siliconerubber, a Kraton™, and a styrene-isoprene-styrene tri-block co-polymertreated with one or more of the following additives: thiuram disulfidederivatives (R′R″ N—(C=5)-S—S—(C=5)-NR′R″), mercaptobenzothiazoles,aminomercaptobenzothrazole (e.g, such as to vulcanized a siliconerubber), sulfides, and azides. Therefore, for example, balloon 4420 mayinclude any of the materials listed above, and may be treated with anadditive such as by treating balloon outer diameter 4428 with one ormore of the additives mentioned above.

Finally, in accordance with embodiments, outer diameter 4428 of balloon4420 may be bonded to an inner diameter of a plurality of fused layersof ePTFE. For example, FIG. 45 is a cross-section view of a cannula anda lined ePTFE balloon. FIG. 45 shows balloon 4520 having a plurality offused layers of ePTFE 4510 with inner diameter 4538 of the ePTFE layersbonded to outer diameter 4428 of balloon liner 4420. According to someembodiments, balloon liner 4420 described below as a liner for balloon4520 may be balloon 4420 described above for FIG. 44, or any of balloons308, 314, 510, 2112, 2204, 2250, 2547, 2647, 3047, 3147, 3522, 3604,3704, 3804, 3947, 4004, 4520, 4820, 8810, 9510, 9110, 9210, 9310, 9910,9920.

According to some embodiments, balloon 4520 may have a property suchthat when inflated balloon 4520 will expand in size to an outer diametersufficient for occlusion of a blood vessel at an inflation pressure (orat an inflation volume with respect to balloon 8810 or apparatus 9700 or9800 of FIGS. 75A-81) and less than sufficient to cause an axial forceon an inner diameter of the blood vessel. For instance, FIG. 45 showsballoon 4520 inflated to outer diameter D2 sufficient for occlusion ofblood vessel 4490 at inflation pressure PR, which is a pressure lessthan sufficient to cause an axial force, such as a force in directions4487, on inner diameter 4492 of blood vessel 4490. Note that accordingto some embodiments, a pressure less than sufficient to cause an axialforce, includes a pressure less than sufficient to cause an axial forceof more than 25 percent of the radial pressure caused by a balloon onthe inner diameter of a blood vessel.

More particularly, balloon 4520 may include a property such that wheninflated to volume V2, balloon 4520 will expand in size to outerdiameter D2 that is approximately inner diameter DV of blood vessel 4490at inflation pressure PR, which is a pressure less than sufficient toexert an axial strain on blood vessel 4490 in directions 4487. Thus,balloon 4520 may be a high-compliance or low-tension balloon, such as aballoon that expands radially and longitudinally upon inflation or formsa plurality of radial outer diameters during inflation and deflation,but does not form wings. In addition, according to some embodiments,pressure PR may be a pressure sufficient to cause balloon 4520 toocclude the blood vessel without radially expanding the blood vessel.

In addition, in accordance with embodiments, fused layers of ePTFE 4510may include one or more layers of ePTFE windings. For example, fusedlayers of ePTFE 4510 may include one or more layers of ePTFE windingswound over each other in concentric, overlaying, intersecting, orcriss-cross patterns, wound according to a process, such as is describedbelow with respect to FIG. 46. Specifically, an ePTFE winding may be oneor more strips or ribbons of ePTFE material greater in length than inwidth, where the width of the material is less than or equal to thedistance between proximal coupling 4422 and distal coupling 4424 asshown in FIG. 45. Thus, windings of ePTFE material may be supplied fromspools, such as spools for storing or supplying ribbon, cloth material,or tape. Also, it is contemplated that fused layers of ePTFE 4510, orwindings of ePTFE material may be porous or may include a property suchthat the layers or windings of ePTFE do not stretch or have a limitedability to stretch axially, or with respect to the width of the fusedlayers of ePTFE or ePTFE windings. Thus, during inflation or deflation,balloon 4520 may include a property such that fused layers of ePTFE 4510expand and contract radially but have no substantial expansion orcontraction axially. Note that according to some embodiments, nosubstantial expansion or contraction axially, includes not expanding orcontracting axially in length by a distance of more than 5 percent ofthe outer diameter distance of the layers. For example, fused layers ofePTFE 4510 may expand and retract in directions 4489 but have nosubstantial expansion axially in directions 4487 as shown in FIG. 45.Moreover, for the embodiment shown in FIG. 45, it is contemplated thatballoon liner 4420 may expand and contract axially in directions 4487 aswell as radially in directions 4489.

Thus, according to some embodiments, balloon 4520 may have a property tocause balloon 4520 to have a post-inflation deflated outer diameter thatretracts to within 20% of a pre-inflated outer diameter of balloon 4520.Specifically, balloon liner 4420 may cause balloon 4520 to retract whendeflated to a post-inflated deflated outer diameter DP that isapproximately 440% greater than the pre-inflated outer diameter DM ofballoon 4520. Moreover, balloon 4520 may include a property such thatduring inflation outer radial surface 4528 of balloon 4520 is parallelto the axis of cannula 4410, and surface 4528 expands radially indirections 4489 but has no substantial expansion axially in directions4487, or along a direction parallel to the axis of cannula 4410.

Similarly to balloon 4420 of FIG. 44, fused layers of ePTFE 4510 mayinclude a property such that during inflation and deflation, fusedlayers of ePTFE 4510 form a plurality of radial outer diameters, such asdiameters DM, D2, and DP, but do not form wings. Also, balloon 4420 orballoon 4520 may include a property such that inflated outer diameter D2approximates an inner diameter of a coronary sinus of a subject at atreatment region and may be sufficient in diameter to make a pressurewaveform of fluid in a coronary sinus or blood vessel becomeventricularized. Specifically, balloon 4420 or balloon 4520 may have anouter diameter D2 sufficient to make pressure waveform 4486 of fluid4480 in blood vessel 4490 become ventricularized. It is alsocontemplated that diameter D2 may be a diameter sufficient to expand aninner diameter of a blood vessel without damaging or bursting the bloodvessel. In other embodiments, inflated outer diameter D2 of balloon 4420or balloon 4520 may expand inner diameter DV of blood vessel 4490sufficient to increase the permeability of a wall of blood vessel 4490to a treatment or biological agent infused into the blood vesselproximate or super-adjacent to the balloon (e.g., such as a treatmentagent described herein, infused at treatment region 4496).

In embodiments, balloon 4520 may have a pre-inflated outer diameterbetween three mm and five mm at a pressure of between zero and oneatmosphere (e.g., such as approximately zero atmospheres), and a ballooninflated outer diameter D2 between seven mm and eleven mm inflationpressure PR, of between six and eight atmospheres. Embodiments ofballoon 4520 also include a balloon having inflated outer diameter D2 ina range of between five mm and nine mm in diameter at a pressure of lessthan six atmospheres.

Likewise, according to some embodiments, balloon 4420, or balloon 4520may have an outside diameter growth rate such as that shown in FIG. 55.Specifically, for an inflation pressure between two and six atmospheres,balloon 4420 or balloon 4520 may include a property such that theballoon will inflate to increase in outer diameter by at least 15% indiameter as compared to a prior outer diameter, for each one atmosphereincrease in inflation pressure. Notably, the semi-linear relationshipbetween outer diameter and inflation pressure as shown in FIG. 55 forballoon 4420 or balloon 4520 allows a balloon to be calibrated todetermine an amount or volume of liquid, such as volumes V1 or V2, forproviding a desired inflation pressure, such as pressure PR. Thus, oncea calibration curve of inflation volume versus inflation pressure for aballoon for various inflation volumes of liquid is created, it ispossible to select a desired inflation pressure and determine the amountor volume of liquid required to provide that desired pressure. Then, theballoon may be inserted into a subject, such as via percutaneousinsertion as described herein, and filled with the predetermined volumeof fluid to provide the desired inflation pressure. Therefore, thevarious configurations of balloon 4420 or balloon 4520 described hereincan be used to occlude a blood vessel, such as an artery or vein in thehuman heart as is described herein. Furthermore, according to someembodiments, cannula 4410 of FIGS. 44 and 45 may be a guide catheter, adelivery catheter, or a guidewire, such as described herein.

In addition, according to some embodiments, various appropriateprocesses may be used to form a lined ePTFE balloon or an ePTFEcomposite balloon, such as balloon 4520. For example, FIG. 46 is a flowdiagram of a process for forming a lined ePTFE balloon. At block 4610, aballoon liner is formed, such as by forming balloon 4420 as describedabove.

At block 4620, layers of ePTFE are wound onto a large mandrel, such asby wrapping ePTFE windings, as described above, around a mandrel havinga diameter in a range of between 10 mm and 12 mm in diameter. Accordingto some embodiments, the diameter of the large mandrel may be selectedto be a diameter that is in a range between one mm and two mm largerthan the desired diameter of the lined ePTFE balloon when inflated.Specifically, for example, a 10 mm diameter large mandrel may be usedwhen forming a lined ePTFE balloon, such as balloon 4520, to have aninflated diameter D2 of 9 mm. Likewise, a mandrel of 11 mm may be usedto produce a lined ePTFE balloon having an inflated diameter of 12 mm.

In addition, according to some embodiments, the layers of ePTFE may beformed by ePTFE windings, strips, or ribbons, such as those describedabove for fused layers of ePTFE 4510. For instance, windings of ePTFEmaterial may be wound onto a large mandrel to form multiple layers ofePTFE that overlay, intersect, are concentric with, or criss-cross otherwindings or layers of ePTFE in various patterns and at various angles.Thus, fused layers of ePTFE 4510 may include one layer of ePTFE windingswound over another layer of ePTFE windings such that the one layer ofwindings forms an “X” pattern, a “W” pattern, a “S” pattern, or acriss-cross pattern. For example, FIG. 47 is an elevated cut-away viewof layers of ePTFE windings. As shown in FIG. 47, first ePTFE windings4710 and 4712 are wound over second ePTFE windings 4720 and 4722, suchthat first ePTFE windings 4710 and 4712 are at an angle, as shown byangle N of between 30° and 120° with respect to second ePTFE windings4720 and 4722. Specifically, in FIG. 47, angle N is 90°. However, it iscontemplated that angle N may be various other angles between 30° and120° such as, an angle of 35°, an angle of 45°, an angle of 60°, anangle of 90°, or an angle of 115°.

Besides winding ePTFE windings in various patterns to form ePTFE layers,various numbers of ePTFE layers may be wound or formed as necessary toensure that there are enough layers to ensure that the ePTFE layers orwindings do not come apart or separate (e.g., such as during inflationand deflation), but not so many ePTFE windings or layers that expansionis inhibited beyond a desired inflation diameter of expansion. Forinstance, when forming plurality of fused ePTFE layers 4510, asufficient number of ePTFE layers may be wound or formed such that whenballoon 4520 is completed, fused ePTFE layers 4510 do not separate whenePTFE balloon 4520 is inflated to inflation pressure PR of between 6 and8 atmospheres in pressure. More particularly, as shown in FIG. 47, afirst ePTFE layer having first ePTFE windings 4710 and 4712 may beformed over a second ePTFE layer having second ePTFE windings 4720 and4722 to form balloon 4520 such that when balloon 4520 is inflated firstePTFE windings 4710 and 4712 do not separate from second ePTFE windings4720 and 4722. Moreover, according to some embodiments, sufficient ePTFElayers and windings may be provided so that ePTFE layers or windings donot separate along seams, such as seam 4730 between first ePTFE windings4710 and 4712. Although FIG. 47 shows only two ePTFE layers, it iscontemplated that fused ePTFE layers 4510 may include more than twolayers, such as by including three layers, four layers, five layers, sixlayers, seven layers, or 10 layers. Thus, for instance, block 4620 mayinclude windings between two and six ePTFE layers in a single directionin a “bandage” wrapped style so that seams between ePTFE windings in asingle layer are bonded or super-adjacent to each other.

At block 4630, layers or windings of ePTFE, such as from block 4620, arefused together, such as by heating the layers or windings wound onto thelarge mandrel. For instance, layers of ePTFE wound onto a large mandrelmay be heated at a temperature between 350° C. and 400° C. for aduration of greater than 10 minutes and less than 60 minutes, asnecessary to sinter the plurality of ePTFE layers or windings. Thus,plurality of fused ePTFE windings 4510 may include windings such asfirst windings 4710 and 4712 wound over second windings 4720 and 4722onto a large mandrel and heated to a temperature of approximately 380°C. for a duration of between 20 and 30 minutes so as to fuse firstwindings 4710 and 4712 to each other and to second windings 4720 and4722. After fusing, fused ePTFE layers may be removed from the largemandrel.

At block 4640, the fused layers of ePTFE are stretched onto a smallmandrel. For instance, a small mandrel may be placed within an innerdiameter of the fused ePTFE layers and the fused ePTFE layers may thenbe stretch apart along the axis of the small mandrel sufficiently sothat the ePTFE layers are stretched onto, touch, or conform to the smallmandrel. Thus, a distal end and a proximate end of the fused ePTFElayers may be gripped or connected to and stretched apart in oppositedirections until the fused layers of ePTFE are stretched sufficiently asdescribed above. After the fused layers are sufficiently stretched, theymay be stabilized by heating. For example, the layers may be stabilizedover a set temperature and time, such as by heating to a temperature of380° C. for a duration of between 30 seconds and two minutes in duration(e.g., such as for approximately one minute). Moreover, according tosome embodiments, the outer diameter of the small mandrel may beselected to be a diameter in a range of between two mm and three mmlarger than the desired deflated diameter of a lined ePTFE balloonbefore inflation. For example, the small mandrel may have an outerdiameter between two and three mm larger than deflated diameter DM ofballoon 4520.

At block 4650, the stretched fused layers of ePTFE are compactedaxially, such as by being compacted in directions opposite of directions4487. For instance, fused layers of ePTFE stretched onto a small mandrelmay then have their outer diameter wrapped with a TEFLON™ tape, a“plumbers” tape, or maybe constrained with a steel tube. Then thewrapped or constrained layers of ePTFE may be compacted axially so thatthe wrapping or constraining of their outer diameter controls expansionof the outer diameter during compacting. For instance, according to someembodiments, compacting includes sufficiently compacting axially inwards(e.g., such as in directions opposite of directions 4487) a distal endand a proximate end of the stretched fused layers of ePTFE, such thatduring inflation of the lined ePTFE balloon (e.g., such as duringinflation of balloon 4520 to inflation pressure PR), the compactedstretched fused layers of ePTFE (e.g., such as fused ePTFE layers 4510)may not expand axially (e.g., such as by being incapable of expanding indirections 4487). Moreover, according to some embodiments compacting mayinclude sufficiently compacting axially inwards a distal end and aproximate end of the compacted stretched fuses of ePTFE such that duringinflation of the lined ePTFE balloon (e.g., such as described above) thecompacted stretched fused layers of ePTFE (e.g., such as fused ePTFElayers 4510) may expand axially (e.g., such as in directions 4487) by aselected percentage of an axial size of the compacted stretched fusedlayers of ePTFE, during inflation of the lined ePTFE balloon. Hence,more particularly, the stretched fused layers of ePTFE may be compactedsufficiently at block 4650 so that during inflation of balloon 4520,fused ePTFE layers 4510 may expand axially in directions 4487 by aselected percentage of the length of the compacted stretched fusedlayers of ePTFE along the longitudinal axis of the small mandrel.

Furthermore, according to some embodiments, compacting may includecompacting sufficiently to reduce the porosity of the windings or layersof ePTFE. After compacting, it is contemplated that the compactedstretched fused layers of ePTFE be stabilized over a set temperature andtime, such as is described above for stabilizing the fused stretchedlayers of ePTFE with respect to block 4640. After stabilizing theTEFLON™ tape, “plumbers” tape, or tube may be removed from the ePTFElayers and the ePTFE layers may be removed from the small mandrel.

Moreover, it is contemplated that the large mandrel or small mandrelassociated with blocks 4620 and 4640 may be tapered so that the linedePTFE balloon formed has a tapered profile, such that when inflated, theballoon with expand in size to a first outer diameter at a firstposition and a different second outer diameter at a different secondposition. Thus, the large mandrel and the small mandrel may be selectedto have a tapered profile so that ePTFE layers have a tapered profileand form lined ePTFE balloon 4520 that when inflated will expand in sizeto a first outer diameter at first axial distance 4432 from distal end4414 of the cannula and will expand in size to a different second outerdiameter at different second axial distance 4434 from distal end 4414 ofthe cannula, such as to provide a tapered profile similar to that shownin FIG. 39.

At block 4660, the layers of ePTFE may be bonded to a balloon liner toform a lined ePTFE balloon, such as balloon 4520. It can be appreciatedthat an inner diameter of the compacted stretched fused layers of ePTFEmay be chemically modified before bonding to a balloon liner.Specifically, inner diameter 4538 of ePTFE layers 4510 may be modifiedwith a plasma polymerization of acrylic acid or a chemical etch ofsodium naphthalene before being bonded to balloon 4420. Moreover, it isconsidered that bonding may include vulcanizing an inner diameter of thecompacted stretched fused layers of ePTFE to a liner having an outerdiameter of silicone rubber material. Also, according to someembodiments, bonding may include hydrogen bonding an inner diameter ofthe compacted stretched fused layers of ePTFE with a balloon linerhaving an outer diameter of polyurethane material.

Likewise, in embodiments, bonding may include bonding an inner diameterof the compacted stretched fused layers of ePTFE with a balloon linerhaving an outer diameter of material such as materials described abovefor forming balloon 4420 or treated of modified with additives, such asadditives described above with respect to balloon 4420. Specifically,chemical modifications to an outer diameter of a balloon liner, such asballoon 4420, are considered before bonding the balloon liner to thecompacted stretched fused layers of ePTFE.

According to various embodiments, the bonding at block 4660 may includeinserting a balloon liner, such as balloon 4420, into the inner diameterof the compacted stretched fused layers of ePTFE, such as into innerdiameter 4538 of fused layers of ePTFE 4510. Then, the outer diameter ofthe compacted stretched fused layers of ePTFE, such as outer diameter4528 may be constrained with, for example, a TEFLON™ tape, a “plumbers”tape, or a steel tube. Next, the balloon liner, such as balloon 4420,may be inflated to cause an outer diameter of the balloon liner, such asouter diameter 4428, to contact or bond to the inner diameter of theconstrained compacted stretched fused layers of ePTFE, such as innerdiameter 4538. For example, the balloon liner may be inflated to aninflation pressure of between 10 and 50 psi, such as to approximately 30psi. Next, it is contemplated that the constrained compacted stretchedfused layers of ePTFE, such as layers of ePTFE 4510, may be heatedsufficiently to bond the outer diameter of the balloon liner, such asouter diameter 4428, to the inner diameter of the compacted stretchedfused layers of ePTFE, such as inner diameter 4538. For example, thelayers of ePTFE may be heated such as described with respect tostabilizing the layers of ePTFE with respect to block 4640.

After bonding the liner to the layers of ePTFE, the constraining tape orsteel tube can be removed and the resulting lined ePTFE balloon can beattached to a cannula. For example, at block 4670, lined ePTFE balloon4520 may be attached to cannula 4410 such as by methods for attachingocclusion devices to a cannula as described herein. Specifically,proximal end 4422 or distal end 4424 of balloon 4420 or balloon 4520 maybe attached to cannula 4410 using one of an adhesive, a crimping bond, alaser bond, and a heat bond, such as to bond proximal end 4422 or distalend 4422 to surface 4416 of cannula 4410. Moreover, it is contemplatedthat such bonding may include ultraviolet (UV) light adhesive or UVthermal bonding. Finally, it is considered, that cannula 4410 may be acannula described herein, such as including a guide catheter, deliverycatheter, or guidewire.

Also, in embodiments, occlusion or filter devices 720, 2006, 2104, 4108,4304 as described herein; balloons 308, 314, 510, 2112, 2204, 2250,2547, 2647, 3047, 3147, 3522, 3604, 3704, 3804, 3947, 4004, 4420, 4520,4820, 8810, 9510, 9110, 9210, 9310, 9910, 9920 as described herein; andany other catheter, cannula, tube, sheath, balloon or occlusion device,may be formed of material including a polymer material, such as apolyurethane-silicone blend (e.g., for example, PurSil™), a homopolymerof an olefin, or a co-polymer of an olefin and one or more othermaterial(s). In various embodiments, a filter device, catheter, cannula,tube, sheath, or balloon or occlusion device, may have a coating appliedto its inside or outside surface, such as, for example, a hydrophiliccoating.

Additionally, in various embodiments, a filter device, catheter,cannula, tube, sheath, balloon or occlusion device, may be made of orinclude a material that minimizes allergic reactions or providesimproved control of expansion outer diameter during inflation anddeflation. For instance, such a balloon can be used in a vessel having adiameter range of about four mm to about nine mm diameter. Moreover,such a filter device, balloon, or occlusion device may be designed orformed to have a larger distal outer diameter and a smaller proximalouter diameter when inflated (e.g., be thicker distally in outerdiameter when inflated and thinner proximally). Specifically, such afilter device, balloon, or occlusion device may have a conical shape.

In various embodiments, a balloon as mentioned herein may be placed in ablood vessel, such as the coronary sinus or a cardiac vein. For example,a balloon can be advanced to a location in the great cardiac vein, abranch of the great cardiac vein, the middle cardiac vein, the smallcardiac vein, or a coronary artery. Thus, the coronary sinus or thecardiac vein may be elastic in nature, so the balloon may prevent vesselhematomas or occlusion of adjacent coronary artery by functioning as asealer, and not a dilator. In various embodiments, the balloon is verycompliant, achieving occlusion at low pressure for a range of vesselsizes. For example, a diameter of the coronary sinus may range fromabout 6.5 mm to about 11 mm, a diameter of the great cardiac vein mayrange from about 4.0 mm to about 7.5 mm, and the diameter of a branch ofthe great cardiac vein may range from about 2.5 mm to about 5.0 mm.

It is also considered that a balloon may be placed in a blood vessel,such as the coronary sinus or a cardiac vein. For example, a balloondescribed herein may be advanced to a location in the great cardiacvein, a branch of the great cardiac vein, the middle cardiac vein, orthe small cardiac vein, or a coronary artery to occlude the vesselbefore the infusion or retro-infusion of a fluid or treatment agent. Inthis embodiment, the balloon is able to extend if the vessel is enlargedduring the infusion or retro-infusion and maintain occlusion of thevessel.

In some embodiments, a balloon may be made from or include material suchas a polyether block amide, a polyetheramide, and mixtures thereof.Similarly, a balloon may be made from or include a polymer having astructure of a regular linear chain of rigid polyamide segmentsinterspaced with flexible polyether segments. In an embodiment, aballoon may be made from or include a polymer or a mixture of two ormore of the polymers having the tradename PEBAX® (a registered trademarkof ATOCHEM), for example Pebax 63D and 55D, or for example one or morePEBAX® polymers having a Shore D hardness less than 70D. In anembodiment, a balloon as described herein, such as for occluding a bloodvessel may be made from or include a polymer or a mixture of two or moreof the polymers represented by the formula:

(Where PA represents a polyamide segment, and PEth represents apolyether segment, and “n” represents an integer of at least one.)

In an embodiment, a balloon to be inflated to a selected inflationpressure or volume may occlude a blood vessel at a pressure of about 0.5to about five atmospheres. In another embodiment, a balloon may achievea growth rate greater than about 40% while maintaining a pressure belowfour atmospheres or even below one atmosphere. Here, the balloonpressure is kept low despite an increase in diameter because of theelasticity of the balloon material. In an embodiment, the balloon mayhave an expanded outer diameter between about 1.5 millimeters (mm) andabout 18 mm when inflated. Moreover, the balloon may have a double wallthickness between about 0.0003 and about 0.0038 inches or a minimum hoopstrength of at least about 23,000 pounds per square inch (psi). Inanother embodiment, the balloon may be either heat bonded, laser bonded,shrink tube or wrap bonded, or attached with an adhesive to a catheter,cannula, port, lumen, or tube as described herein.

In some embodiments, a balloon or occlusion device, may be a highcompliance low pressure balloon. For example, FIG. 48 is a cross sectionview of a cannula and a high compliance low pressure balloon. As shownin FIG. 48, cannula 4810 (e.g., such as a cannula having a dimensionsuitable for percutaneous advancement through a blood vessel, such asadvancement in direction 4885 through blood vessel 4890), includesproximal end 4812, distal end 4814, and exterior surface 4816. FIG. 48also shows balloon 4820 axially connected to exterior surface 4816 ofcannula 4810, at or adjacent distal end 4814. FIG. 48 shows cannula 4810having diameter of cannula DC, and balloon 4820 having minimal wingdiameter DM, and balloon outer first diameter D1. Blood vessel 4890 isshown having diameter of vessel DV and fluid 4880 (e.g., such as bloodor treatment agent). Balloon 4820 may be a balloon, occlusion device, orfilter device such as described herein.

Furthermore, according to some embodiments, balloon 4820 may includematerial or matter having a polymer moiety represented by the formula

wherein PA represents a polyamide moiety, and PEth represents apolyether moiety, and “n” represents an integer of at least one. Inaddition, according to some embodiments, balloon 4820 may include athermoplastic blend copolymer material having one of a polyether blockamide resin moiety and a polyetheramide moiety. In addition, accordingto some embodiments, balloon 4820 may be restricted or restrained fromexpansion or inflation, such as by a sheath (e.g., such as sheath 790described above for FIGS. 7-10), to have first diameter D1.

According to some embodiments, balloon 4820 may have a property suchthat balloon 4820 will inflate, such as in directions 4886 and 4888 as aresult of pressures 4830 and 4832 increasing balloon first volume V1, toan inflated balloon outer second diameter that will occlude a bloodvessel. For example, FIG. 49A is a cross sectional view of a cannula anda balloon inflated to occlude a blood vessel. As shown in FIG. 49A,balloon 4820 is inflated to second diameter D2 that will occlude bloodvessel 4990, such as by substantially preventing fluid 4980 from flowingin blood vessel 4890 past balloon 4820 in direction 4985. Likewise, FIG.49A shows balloon 4820 inflated to have volume V2, and exert pressure PRon an inner diameter of blood vessel 4890.

Consequently, according to some embodiments, balloon 4820 may include aproperty such that balloon 4820 can achieve a volumetric expansion(e.g., such as by expanding from first volume V1 to second volume V2) ofgreater than about 40% during inflation. Specifically, balloon 4820 mayhave a property such that it may inflate according to the growth ratechart of FIG. 55. Moreover, balloon 4820 may be able to expand orinflate to an inflated outer diameter, such as second diameter D2,between 1.5 millimeters and 18 millimeters in diameter. Likewise,according to some embodiments, balloon 4820 may be inflated to seconddiameter D2 to occlude blood vessel 4890 at a predetermined pressure,such as pressure PR, of between 0.5 atmospheres and 5.0 atmospheres ofpressure. More particularly, balloon 4820 may include a property suchthat it will inflate to a predetermined pressure, such as pressure PR,sufficient to make a pressure waveform in a blood vessel becomeventricularized. For example, balloon 4820 may inflate to apredetermined pressure to make a pressure waveform of blood or fluid,such as fluid 4980, traveling in direction 4985 become ventricularized.Thus, balloon 4820 may be inflated to a predetermined volume, such assecond volume V2, or a predetermined inflated outer diameter, such assecond diameter D2.

Furthermore, balloon 4820 may have deflated a double wall thicknessbetween 0.0003 and 0.0038 inches in thickness. For example, FIG. 49B maybe a cross sectional view of FIG. 49A from perspective “A”, according toan embodiment. FIG. 49B shows single wall thickness T of balloon 4820,wherein T is ½ of the double wall thickness. Moreover, according to someembodiments, balloon 4820 may have a minimum hoop strength of at leastabout 23,000 psi strength. Also, balloon 4820 may include a propertysuch that the balloon will have a durometer hardness of between 50 ShoreD and 70 Shore D. Next, balloon 4820 may be axially connected to anexterior surface of a cannula, such as cannula 4810, wherein the cannulamay be a guide cannula, a delivery cannula, or a guide wire as describedherein.

FIG. 49B also shows cannula 4810 having lumens 4912, 4914, and 4940.Lumen 4912 may be a lumen such as lumen 1712 described above for FIG.17. Lumen 4914 may be a lumen such as lumen 1812 described above forFIG. 18. Lumen 4940 may be a lumen such as lumen 1740 described abovefor FIG. 17. It is also considered any of that lumens 4912, 4914, and4940 may be similar to a guidewire lumen, accessory lumen or pressurelumen as described herein.

According to some embodiments, balloon 4820 may include a property suchthat the balloon will deflate, such as in directions 4986 and 4988 as aresult of pressures 4930 and 4932 to reduce second volume V2, to apost-inflated deflated balloon outer third diameter. For example, FIG.50 is a cross sectional view of a cannula and a postinflated deflatedballoon. As shown in FIG. 50, balloon 4820 is postinflated deflated tothird volume V3 and third diameter D3. Specifically, balloon 4820 may bedeflated to third diameter D3 that will allow balloon 4820 to bewithdrawn from a blood vessel, such as withdrawn in direction 4985 fromblood vessel 4890. Consequently, postinflated deflated volume of balloon4820, such as third volume V3 may be approximately equal to preinflatedvolume of balloon 4820, such as volume V1.

Furthermore, according to some embodiments, balloon 4820 may include aproperty such that it has at least three wings before being inflated andafter being deflated. For example, FIG. 51 may be a cross sectional viewof FIG. 48 from perspective “A”, according to an embodiment. FIG. 51shows balloon 4820 having wings 4852, 4854, and 4856 before balloon 4820being inflated. Moreover, each wing has a wing length defined by thelength of a line extending within the wing along a medial axis of across-section of the wing. For example, FIG. 51 shows wing 4852 havingwing length one WL1 defined by the length of a line extending withinwing 4852 along a median access of a cross section of wing 4852, such asshown by wing length one WL1 in FIG. 51.

In addition, balloon 4820 includes a property such that the wings ofballoon 4820 are subsumed into the outer diameter of balloon 4820 wheninflated. For example, FIG. 52 may be a cross sectional view of FIG. 49Afrom perspective “A”, according to an embodiment. FIG. 52 shows balloon4820 having outer balloon diameter 5228 when inflated, and seconddiameter D2 which is approximately equivalent to that of or at leastequivalent to that of an inner diameter of a blood vessel at a treatmentregion. Thus, second diameter D2 may be approximately equivalent to orat least equivalent to diameter of vessel DV of blood vessel 4890.Moreover, according to some embodiments, second diameter D2 may be adiameter sufficient to occlude a blood vessel, such as blood vessel4890.

Further, balloon 4820 may include a property such that the balloon willhave at least three wings before being inflated and after beingdeflated, wherein a pre-inflated wing length for each wing isapproximately equal to a post-inflated deflated wing length for eachwing. For example, FIG. 53 may be a cross sectional view of FIG. 50 fromperspective “A”, according to an embodiment. FIG. 53 shows postinflateddeflated wing length two WL2 of wing length 4852 being a wing lengththat is approximately equal to preinflated wing length one WL1. Thus,although balloon 4820 is shown before inflation in FIG. 49A and afterbeing inflated and deflated in FIG. 53, the wing length of wing 4852before inflation is approximately equal to that for wing 4852 afterbeing inflated and deflated.

However, according to some embodiments, balloon 4820 may include aproperty such that an outer diameter point farthest away from the accessof cannula 4810 for each wing is approximately 30% greater for thepostinflated deflated wing than it is for the preinflated wing. Forexample, FIG. 51 shows wing 4852 having outer diameter point one P1defined by a point of wing 4852 radially farthest away from axis of thecannula AC, and wing diameter one DW1 defined by a length of a straightline extending from axis of cannula AC, radially out to the outerdiameter point one P1. Similarly, FIG. 53 shows wing 4852 after beinginflated and deflated having outer diameter point two P2 defined by apoint of the wing radially farthest away from axis of the cannula AC,and a wing diameter two DW2 defined by a length of a straight lineextending from axis of the cannula AC, radially out to outer diameterpoint two P2. Thus, according to some embodiments, preinflated wingdiameter DW1 for wing 4852 is approximately 30% less than postinflateddeflated wing diameter DW2 of wing 4852. Hence, although the wing lengthfor a postinflated deflated wing is approximately equal to that of apreinflated wing, the wing diameter for a postinflated deflated wing maybe greater than that for a preinflated wing, such as in a range between10% and 50% greater in wing diameter.

Therefore, the various configurations of balloon 4820 and lumen 4810described herein can be used to occlude a blood vessel, such as by usinga high compliance low pressure balloon for balloon 4820, as describedabove. For example, FIG. 54 is a flow diagram of a process for using aballoon (e.g., such as any balloon or occlusion device described herein,including embodiments of balloon 4820 described with respect to FIGS.48-53 and views thereof) to occlude a blood vessel (e.g., such as aprocess that may be used with system controller 3080, or a treatmentprocess for infusion of a treatment agent into an artery or vein of apatient using devices, apparatus, methods, or processes described herein(e.g., such as according to the process described with respect to FIG.3, 19, 54, 55, 63, or 82). At block 5410 a cannula, such as cannula4810, is advanced percutaneously through a blood vessel, such as bloodvessel 4890, wherein a balloon, such as balloon 4820, is axiallyconnected to an exterior surface of the cannula at or adjacent thedistal end of the cannula. It is contemplated that the cannula may beadvanced via a retrograde advancement, such as by being pushed up ablood vessel with or against a flow of blood, such as from one vesselinto a smaller vessel to provide retrograde infusion treatment.Specifically, the cannula may be advanced to a treatment region such asa region in a coronary sinus or vein of a subject (e.g., such astreatment region 4996).

At block 5420, the balloon is inflated to between 0.5 atmospheres and5.0 atmospheres of pressure. For example, balloon 4820 may be inflatedso that first diameter D1 is increased to second diameter D2, asdescribed above. Also, according to some embodiments, balloon 4820 maybe inflated by inflating to an expansion pressure of between twoatmospheres in pressure and six atmospheres in pressure applied to aninner diameter of a blood vessel, such as diameter of vessel DV, at atreatment region such as region 4996. Moreover, according to someembodiments, balloon 4820 may be inflated to a predetermined volume(e.g., such as volume V2), a predetermined second diameter in a rangebetween four millimeters and 17 millimeters in diameter (e.g., such assecond diameter D2), or a predetermined pressure of between 0.5atmospheres and six atmospheres in pressure (e.g., such as pressure PR).

At block 5430 the blood vessel is occluded. Specifically, balloon 4820may be inflated to expand first diameter D1 to second diameter D2 untilsecond diameter D2 approximates an inner diameter of a coronary sinus ora coronary blood vessel of a subject at a treatment region or untilsecond diameter D2 is sufficient to make a pressure waveform of fluid inthe coronary sinus or coronary vein become ventricularized, such as isdescribed herein.

At block 5435 a treatment agent is delivered, such as to a treatmentregion. For example, a treatment agent may include infusion pellets,suspended cells, stem cells, microspheres, blood cells, drugs, orvarious other appropriate liquids and materials as described herein.Likewise, it is contemplated that such treatment agents may be deliveredto treatment region 4996, such as by being delivered as part of or asall of liquid 4980. Note that it is contemplated that balloon 4820 maybe inflated or deflated using fluids, including fluids described hereinas a treatment agent.

At block 5440 the option of aspirating a treatment region is provided.For example, treatment region 4996 may be aspirated such as by a hole indistal end 4814 of cannula 4810 or via a hole through exterior surface4816 of cannula 4810 at distal end 4814. Specifically, for instance,liquid 4980 may be aspirated as described above with respect to hole 988for FIG. 9. Thus, as shown in FIG. 49, liquid 4980 in treatment region4996 may optionally be aspirated. It is contemplated that liquid 4980may include a drug, treatment agent, infusion pellets, suspended cells,stem cells, microspheres, or various other appropriate liquids ormaterials as mentioned herein.

At block 5450 balloon 4820 is deflated, such as described herein. Forexample, balloon 4820 may be deflated to a post inflation deflationvolume, such as third volume V3, approximately equal to a preinflatedvolume, such as first volume V1, of balloon 4820.

At block 5460 cannula 4810 may be retracted, such as to withdraw balloon4820 back out of vessel 4890 and out of the subject.

FIG. 55, illustrates a balloon outside diameter growth rate, such as foran occlusion or filter device (e.g., including devices 720, 2006, 2104,4108, 4304 as described herein), a balloon (e.g., such as balloons 308,314, 510, 2112, 2204, 2250, 2547, 2647, 3047, 3147, 3522, 3604, 3704,3804, 3947, 4004, 4420, 4520, 4820, 8810, 9510, 9110, 9210, 9310, 9910,9920 as described herein), or other balloons or occlusion devices.). Forinstance, FIG. 55 may show the outside diameter growth rate 5510 for aneight mm balloon starting with the uninflated outside diameter, andgrowing to the balloon's inflated outer diameter, where the growth rateis plotted as a function of inflation pressure 5520. FIG. 55 shows aballoon with a growth rate or elasticity of about 25% at a pressure ofabout two atmospheres. In another embodiment, a balloon may have agrowth rate or elasticity of about 40% at a pressure of about 3.5atmospheres.

In various embodiments, balloon outer diameter sizing (e.g., such as toocclude a blood vessel with a balloon) is controlled by monitoringfactors including venous pressure waveform changes distal to theballoon. For instance, inflation of the balloon may be continued until awaveform becomes ventricularized.

FIG. 56 illustrates a graph showing pressure distal to a balloon 6510 ina blood vessel as a function of time 6520 (e.g., such as the pressure attreatment region 996 to be infused with a treatment agent, where thetreatment region may be distal to, or proximal to a balloon occluding ablood vessel.). It is to be appreciated that the process related to FIG.56 may be a process that may be used with a system controller (e.g.,such as a system controller that may access a memory including machinereadable instructions, such as system controller 3080), or a treatmentprocess for infusion of a treatment agent into an artery or vein of apatient using devices, apparatus, methods, or processes described herein(e.g., such as according to the process described with respect to FIG.3, 19, 54, 55, 63, or 82). Reference numeral 6501 illustrates time t1during which a catheters or cannula is advance percutaneously so that adistal end of the catheter or cannula can be located in the coronarysinus or another vessel.

Reference numeral 5602 corresponds to time t2 during which a balloon,such is inflated to occlude the coronary sinus or another blood vessel.The coronary sinus or other blood vessel may be occluded, for example byinflating an occluding balloon or device until the coronary sinus orother blood vessel has a pressure waveform that becomes ventricularized.

Reference numeral 5603, corresponding to time t3 during which atreatment agent, such as described herein, is infused or introduced intothe blood vessel and increases the pressure in the vessel to arelatively higher pressure distal to the balloons (or at treatmentregion 996).

At the conclusion of the infusion period, t3, time t4 referred to byreference numeral 5604, is a period of time where the pressure distal tothe balloon is a lower pressure following infusion, even though thecoronary sinus or other vessel is still occluded by a balloons orocclusion device.

Reference numeral 5605, refers to time t5, during which the occludingballoon or device is deflated, and the catheter or cannula may beremoved so that the perfusion (e.g., such as according to the processdescribed with respect to FIG. 82) or flow of blood or treatment agentcan resume in the coronary sinus or another vessel.

In various embodiments, the plot illustrated in FIG. 56 allows for anefficient treatment agent or drug infusion from a vein or artery totissue to be treated with the possibility of “hands-off” operation. Invarious embodiments, when the pressure waveform changes to a“ventricularized” waveform of venous pressure, a balloon-sizingindicator notifies the operator or control system to stop ballooninflation. After balloon inflation has been stopped, a pressure sensorcan measure the infusion pressure needed for an effective therapeuticdosage of a liquid containing a treatment agent. Infusion of a treatmentagent can be accomplished with auto-infusion with a controller (e.g.,such as controller 3080), or by an operator manually (e.g., such as byapparatus 9700 or 9800 of FIGS. 75A-81).

Suitable treatment agents to be used with catheters or cannula include aliquid carrying one or more treatment agents. In another embodiment, atreatment agent or liquid includes one or more drugs or treatmentagents, such as is used to prevent reperfusion injury. For instance,according to some embodiments, a treatment agent may be or include aliquid having one or more antibodies, for example, the antibodiesagainst CD 11/18, P-selectin, L-selectin, ICAM, or VCAM. In anotherembodiment, the liquid includes IGF-I, estrogen, or GIK solution. Inanother embodiment, the liquid includes drugs like adenosine or itsisoforms, Na/H exchangers, or Na/K exchangers. In another embodiment,the liquid can include cells, for example, cardiomyocites ormulti-potent or ologo-potent cells like stem cells or progenitor cells.Also, the liquid may include angiogenic cells, or other types ofstructural cells like skeletal or smooth muscle cells. In anotherembodiment the liquid includes biological agents or genes, for example,VEGF, FGF, or HGF. In another embodiment, liquid includes one or more ofthe following: Calpain I, insulin, adenosine, antioxidants, glutathioneperoxidase, vitamin E (alpha tocopherol), Na+—H+ exchange inhibitors,caroporide (HOE 642), agents that open K_(ATP) channels, nitric oxide(NO), endothelin receptor antagonists, tetrahydrobiopterin, statins,sevoflurane, propofol, pinacidil, morphine, verapamil, and blends ormixtures thereof.

In an embodiment, a pressure increasing device may be attached tofitting 2632 at proximal end 2626 of catheter 2620 (e.g., see FIGS.26-29, and fitting 3032 at proximal end 3026 of catheter 3020 of FIG.30) to deliver a liquid that is or includes a treatment agent, throughdelivery lumen and to a blood vessel, such as at treatment region 996(e.g., such as via a catheter, cannula, or deliver lumen as describedherein). In various embodiments, the pressure increasing device is asyringe. In embodiments, the pressure increasing device may be a pump(which may or may not include one or more syringes). For example, thepressure increasing device can be a centrifugal pump, a reciprocatingpump, or a gear pump. In various embodiments, the pump is able toachieve a low flow rate at a high pressure. One suitable pump isillustrated in FIG. 57. Centrifugal pump 5700 includes inlet 5702 andoutlet 5704 so that the fluid flows as marked by arrow 5706. Pump 5700has pumphousing 5708 to contain fluid and rotor 5710 which has impeller5712 attached. In various embodiments, impeller 5712 rotates to create acentrifugal force to force fluid from inlet 5702 to outlet 5704 as shownby arrow 5706. Pump 5700 also includes stator 5714 which has winding5716 attached. In various embodiments, rotor 5710 is removably connectedto stator 5714, and there is no direct mechanical connection betweenstator 5714 and rotor 5710. In various embodiments, rotor 5710 andimpeller 5712 are driven by a magnetic force generated by winding 5716.In various embodiments, rotor 5710 and pump housing 5708 are disposable,while stator 5714 and winding 5716 are not disposable. In anotherembodiment, the fluid flows through inlet 5702 to outlet 5704, whichfluid path is sterilized, while stator 5714 and winding 5716 are notsterilized. It is considered that a suitable pump can be a disposableinfusion pump or a magnetically-levitated centrifugal pump with adisposable rotor chamber.

In another embodiment, a suitable pressure increasing device isillustrated in FIG. 58. Pump 5800 includes handle 5820 with batteries5809, and activator button 5810. Connected to handle 5820 is body 5830of pump 5800. Body 5830 includes pressure measurement connection 5808,micro-controller 5805, and motor driver chip 5812. Pump 5800 alsoincludes attachment 5832 with motor 5804, motor coupler 5803, wherecoupler 5803 is connected to lead screw 5802. Lead screw 5802 is fedinto non-rotating threaded coupling 5824, so that when motor 5804 isactivated, rotational force and motion from motor 5804 is transferredthrough coupler 5803 to lead screw 5802 to advance or retractnon-rotating threaded coupling 5824, depending on the direction ofrotation. Non-rotating threaded coupling 5824 is attached to plunger5801, so that when non-rotating threaded coupling 5824 moves, plunger5801 also moves. Plunger 5801 can move distally to make reservoir 5814smaller, or proximally to make reservoir 5814 larger. At the distal endof reservoir 5814 is nozzle 5816 attached to outlet 5818.

In operation, user (not shown) may activate pump 5800 by pressing button5810. Pressing button 5810 causes micro-controller 5805 to activate,which in turn activates motor driver chip 5812 which sends a currentfrom batteries 5809 to motor 5804. This causes motor 5804 to rotate,sending a rotational motion and force through coupler 5803 to lead screw5802. Rotating lead screw 5802 causes non-rotating threaded coupling andplunger 5801 to advance or retract, depending on the rotation of motor5804 and lead screw 5802. Advancing plunger 5801 causes an increase inpressure and a decrease in volume in reservoir 5814 causing fluid or gasstored in reservoir 5814 to be forced through nozzle 5816 and intooutlet 5818. In various embodiments, to maintain a suitable pressure,pressure feedback from the patient may be received into pump 5800through pressure measurement connection 5808, which pressure informationis fed to micro-controller 5805, which activates motor driver chip 5812,to activate motor 5804 to increase pressure, or to deactivate motor 5804to allow pressure to drop, or to reverse the direction of motor 5804 todecrease pressure.

Another suitable pressure increasing device is illustrated in FIG. 59.Pump 5900 includes handle 5920 having batteries 5909, and activationbutton 5910. Handle 5920 is connected to body 5930, which includespressure measurement connection 5908, motor driver chip 5912, andmicro-controller 5905. Connected to body 5930 is attachment 5932 withmotor 5904, coupler 5903, and lead screw 5902. Lead screw 5902 feedsinto non-rotating threaded coupling 5924, which is attached to syringeor abutted against head 5940. Syringe 5922 is located in a suitablyshaped opening, the distal end of handle 5932, and includes syringe head5940, plunger 5901, reservoir 5914, and nozzle 5916. Nozzle 5916 feedsinto outlet 5918. In another embodiment, syringe 5922 may be disposableand thrown away after each treatment. In another embodiment, syringe5922 may be removed and cleaned or sterilized before the next treatment.In some embodiments, the pump, such as pump 5900 may have multiplesyringes with different treatment agents.

In operation, pump 5900 may be activated by a user (not shown) by button5910, which activates micro-controller 5905, which activates motordriver chip 5912, which in turn activates motor 5904, by sending acurrent from batteries 5909 to motor 5904. Motor 5904 rotates coupler5903, which rotates lead screw 5902 to advance or retract non-rotatingthreaded coupling 5924, which serves to advance or retract syringe head5940, respectively. If syringe head 5940 is advanced, plunger 5901 isalso advanced towards the distal end of handle 5932 which serves toincrease the pressure and decrease the volume of reservoir 5914, whichforces fluid or gas stored in reservoir 5914 through nozzle 5916 andinto outlet 5918. If syringe head 5940 is pulled towards proximal end ofhandle 5932, then the pressure in reservoir 5914 is lowered, and thevolume in reservoir 5914 is increased, and fluid may be pulled fromoutlet 5918 through nozzle 5916 and into reservoir 5914. In variousembodiments, a pressure measurement from the patient may be deliveredinto pump 5900 through pressure measurement connection 5908, whichinformation is fed to micro-controller 5905 then into motor driver chip5912 which is used to control motor 5904 to advance or retract syringehead 5940 to raise or lower pressure in reservoir 5914, respectively.

Referring now to FIG. 60, there is illustrated a suitable pressuretransferring device. Pressure transferring device 6000 includes fluidinlet 6002, and fluid outlet 6004. Plunger 6006 is located in device6000, which plunger 6006 serves to separate inlet reservoir 6008 fromoutlet reservoir 6010. As a fluid is pumped into inlet 6002, fluidenters inlet reservoir 6008 and exerts a force upon plunger 6006. Thisforces plunger 6006 distally, which increases the pressure and lowersthe volume of outlet reservoir 6010, which forces the fluid in outletreservoir 6010 into outlet 6004. Conversely, when a fluid is forced intooutlet 6004 and into outlet reservoir 6010, it exerts a force on plunger6006, and forces plunger 6006 proximally, which increases the pressureand lowers the volume of inlet reservoir 6008 and forces the fluid ininlet reservoir 6008 into inlet 6002. Device 6000 serves to equalize thepressures in inlet 6002 and inlet reservoir 6008, with the pressures inoutlet 6004 and outlet reservoir 6010. Device 6000 may be usedimmediately before a catheter, so that a relatively expensive treatmentagent can be placed in outlet reservoir 6010 and outlet 6004, while arelatively inexpensive liquid, for example a saline solution or water,can be placed in inlet reservoir 6008 and inlet 6002, with a pump (notshown) or other pressure increasing device connected to inlet 6002.

Referring now to FIG. 61, is a pressure-maintaining or dampening device6100. Device 6100 has inlet 6102 and outlet 6104. Inside device 6100 isplunger 6106 which serves to seal fluid into pressure reservoir 6112. Asfluid flows from inlet 6102 into pressure reservoir 6112, the fluidexerts a force on plunger 6106 which compresses spring 6108, until theforce exerted by spring 6108 equals the force exerted by the fluid inpressure reservoir 6112 on plunger 6106. When the fluid stops flowingfrom inlet 6102 into pressure reservoir 6112, there will be a fluid flowprovided to outlet 6104 as plunger 6106 is forced down by compressedspring 6108, decreasing the size of fluid reservoir 6112. This downwardmovement of plunger 6106 continues until pressure in pressure reservoir6112 equals downward pressure exerted by spring 6108. In anotherembodiment, spring adjusting device 6110 may be provided to adjust thetension of spring 6108, so that more or less force is required tocompress spring 6108.

Referring now to FIG. 62, is a pressure-maintaining or dampening device6200, with inlet 6202 and outlet 6204. As fluid flows through inlet 6202and into pressure reservoir 6212, the fluid causes reservoir 6212 toforce walls 6208 of device 6200 outwards until the inward force exertedby walls 6208 equals the outward force exerted by fluid in pressurereservoir 6212. When the fluid flow through inlet 6202 stops, fluid flowto outlet 6204 continues until force exerted by walls 6208 equals forceexerted by fluid in pressure reservoir 6212. Walls 6208 may be made of aflexible material, for example rubber. Materials and thickness of walls6208 may be adjusted so that an appropriate pressure may be maintainedwithin fluid reservoir 6212.

Referring now to FIG. 63, is a flow diagram of a process or method oftreating a patient, in accordance with an embodiment. First, a vein isaccessed 6302 by a catheter, for example, the exterior femoral vein, theinterior femoral vein, carotid, jugular, brachial, subclavian, orsaphalic vein is accessed by distal end of a guide catheter. Coronarysinus 6304 is accessed with a guide catheter through either the inferiorvena cava or superior vena cava. Venogram 6306 is performed through theguide catheter to visualize coronary sinus or great cardiac vein.Deployment of guidewire and retroinfusion balloon catheter 6308 into thecoronary sinus through the guide catheter. Venogram 6310 to visualizedistal venus anatomy. Navigation of infusion catheter over guidewire6312 to a target location. Measurement of baseline parameters 6314, forexample, pressure, flow, oxygen saturation, pH, or temperature at thetarget location. Inflate balloon 6316 to occlude coronary sinus or othervessel where balloon catheter has been placed, for example the targetlocation. Perform blush score 6318, an optional step to determine blushpressure. Set infusion parameters 6320, for example, absolute pressure,differential pressure, blush pressure, dosage, or flow rate. Startinfusion 6322. Optional measuring of infusion parameters and feedback toa controller. Stop infusion 6324 when set parameters are satisfied. Holdballoon inflated 6326 for a period of time to allow uptake orsaturation. Deflate balloon 6328. Remove catheter, guide catheter orguidewire, from vessel 6330.

Note that it is contemplated that the process described above withrespect to FIG. 63, any or all of the pressure increasing devices,pumps, pressure transfer devices, or pressure maintaining devicesdescribed herein may be controlled manually, automatically, or by amachine, such as by system controller 3080, or according to a treatmentprocess for infusion of a treatment agent into an artery or vein of apatient using devices, apparatus, methods, or processes described herein(e.g., such as according to the process described with respect to FIG.3, 19, 54, 55, or 82).

In another embodiment, a catheter may be used to locally administer atreatment or therapeutic agent. Copending U.S. Application having Ser.No. 10/246,249 filed on Sep. 18, 2002 discloses suitable treatmentagents and suitable methods of administering the treatment agents.Copending U.S. Application having Ser. No. 10/246,249 filed on Sep. 18,2002 is herein incorporated by reference in its entirety. U.S. Pat. No.6,346,098, issued to Yock et al., discloses a suitable method of locallyadministering a treatment agent. U.S. Pat. No. 6,346,098, issued to Yocket al., is herein incorporated by reference in its entirety.

Note that all embodiments of devices, apparatus, methods, or processesdescribed herein are contemplated to include treatment including by oneor more balloons, occlusion devices, or filter devices (e.g., such asballoon 2647, 3147, 3522, 3947, 2547, 3047, 3604, 3704, 3804, 4004, 308,2204, 2250, 2112, 314, 510, 4420, 4520, 4620, 4820, 8810, 9510, 9110,9210, 9310, 9910, 9920, or other balloons or occlusion devices) that mayhave an outer diameter that is volume controlled (e.g., see balloon8810) or pressure controlled (e.g., see balloons 4520, 4620, and 4820)to expand to, occlude, or filter fluid in a blood vessel (e.g., such asan artery or vein of a human being). For example, an outer diameter maybe volume controlled by controlling the amount of inflation volume of agas (e.g., such as air, carbon dioxide, or a gas having a fluoroscopycontrast agent) or a liquid (e.g., such as water, saline solution, or afluid having a fluoroscopy contrast agent) used to inflate the occlusiondevice. Specifically, an inflation volume may be incrementally increasedby a selected volume amount over a range of total inflation volume tocause the outer diameter of an occlusion balloon to incrementallyincrease by a predictable amount for each incremental increase involume. Thus, equal or unequal incremental increases in inflation volumecan be used to cause equal or unequal increases in occlusion deviceouter diameter, over a desired total diameter range.

For instance, according to some embodiments, additional inflation fluidvolume does not increase pressure because the high compliance balloongrows in outer diameter. Furthermore, according to some embodiments,when the outer diameter reaches a constraint, such as the inner diameterof a blood vessel as described herein, the balloon has a property,dimension, or is configured such that additional inflation fluid volumedoes not increase pressure or force in a direction perpendicular to theouter diameter (e.g., such as in a direction towards the inner diameterof the blood vessel), because the high compliance balloon grows in anaxial direction within the blood vessel. It is also contemplated thatwhen the outer diameter of the balloon reaches a constraint, additionalinflation fluid volume will increase pressure or force in a directionperpendicular to the outer diameter of the balloon, but not appreciably.Specifically, in accordance with an embodiment, additional inflationfluid volume will increase pressure or force in a directionperpendicular to the outer diameter of the balloon by a non appreciableamount, such as by between zero and 10 percent increase in pressure(e.g., where the pressure in a direction perpendicular to the outerdiameter of the balloon may be equal to the inflation pressure withinthe balloon).

For example, FIG. 64A is a cross sectional view of a cannula and aballoon. FIG. 64A shows apparatus 8800 having cannula 8802 with adimension suitable for percutaneous advancement through a blood vessel(e.g., such as blood vessel 990 mentioned herein) and having a cannulaproximal end (not shown, but such as proximal end 9504 shown anddescribed with respect to FIGS. 69A-F) and distal end 8806. FIG. 64B isa cross-sectional view of apparatus 8800 of FIG. 64A from perspective“A”. Cannula 8802 may be a cannula similar to cannula 710 or any othercatheter or cannula. FIGS. 64A and B also show cannula 8802 havingdiameter CRD such as a diameter for a guide catheter, delivery catheter,or guidewire catheter as described herein. Balloon 8810 is axiallyattached to exterior surface 8808 at or adjacent distal end 8806 ofcannula 8802 at proximal attachment 8809 and distal attachment 8811.Balloon 8810 may be a balloon such as a balloon or occlusion device asdescribed herein.

According to some embodiments, balloon 8810 may have a property suchthat when inflated to a plurality of selected increasing inflationvolumes, balloon 8810 forms a plurality of predictably increasing radialouter diameters, and has an inflation pressure that increases by lessthan five percent in pressure while being inflated to the plurality ofselected increasing inflation volumes.

Moreover, balloon 8810 may be is adapted to inflate to an outer diameterin a range of about 2 mm to about 20 mm, such as to occlude a bloodvessel having an inner diameter in a range of between 1.5 mm and 19.5mm. Specifically, balloon 8810 may selected or inflated by a sufficientinflation volume or pressure to inflate to an outer diameterapproximately 0.5 mm greater than the inner diameter of the blood vesselit is to occlude. Thus, balloon 8810 may inflate to an outer diameter ofabout 2 mm to occlude a blood vessel having an inner diameter of about1.5 mm, and may inflate to an outer diameter of about 20 mm to occlude ablood vessel having an inner diameter of about 19.5 mm.

Also shown in FIGS. 64A and B, balloon 8810 has first diameter BRD1,first length BRL1, first inflation volume BRV1 and first inflationpressure BRP1. According to some embodiments first length BRL1 may be aselected preinflated length greater than two millimeters in length, suchas a length of between two millimeters and 30 millimeters, (e.g.,including first length BRL1 equal to three millimeters, between five andsix millimeters, between eight and 10 millimeters, between five and 10millimeters, or greater than 30 millimeters in length). In addition,first diameter BRD1 may be a preinflated outer diameter of between 0.25inches and 0.65 inches in diameter (e.g., such as first diameter BRD1 of0.44 inches) that inflates to expand to an outer diameter of 18millimeter when inflated without bursting or permanently deforming.Next, balloon 8810 may have a preinflated single wall thickness ofbetween 0.001 inches and 0.02 inches in thickness (e.g., such as a wallthickness of 0.003 inches) at a preinflation pressure below oneatmosphere in pressure, such as a preinflation pressure of zeroatmosphere.

FIG. 65A shows the balloon and cannula of FIG. 64A, with the ballooninflated to a second inflation volume. FIG. 65B is a cross-sectionalview of apparatus 8800 of FIG. 65A from perspective “A”. FIGS. 65A and Bshow balloon 8810 inflated to second inflation volume BRV2, secondinflation pressure BRP2, second length BRL2, and second diameter BRD2.For example, second inflation volume BRV2 may be one of a plurality ofselected increasing inflation volumes to cause balloon 8810 to form asecond predictably increasing radial outer diameter, second diameterBRD2, and to have a second inflation pressure, BRP2 that may or may notbe less than five percent greater than first inflation pressure BRP1.

FIG. 66A shows the cannula and balloon of FIG. 65A, with the ballooninflated to a third inflation volume. FIG. 66B is a cross-sectional viewof apparatus 8800 of FIG. 66A from perspective “A”. Balloon 8810 isinflated to third inflation volume BRV3, third inflation pressure BRP3,third length BRL3, and third diameter BRD3. For example, FIGS. 66A and Bshow balloon 8810 inflated to a selected increasing third inflationvolume BRV3 to form predictably increasing radial outer diameter thirddiameter BRD3 and having third inflation pressure BRP3 that may increaseby less than five percent in pressure as compared to second inflationpressure BRP2.

Thus, according to some embodiments, balloon 8810 may be inflated with aplurality of selected increasing inflation volumes increasing from zeroto 2.0 cubic centimeters. In some cases, balloon 8810 may be inflatedwith a plurality of selected increasing inflation volumes that includingincreasing inflation volume from 0.05 cubic centimeters to 0.2 cubiccentimeters by steps of additional controlled volumes in increments ofbetween 0.005 cubic centimeters in volume and 0.05 cubic centimeters involume (e.g., such as 0.01 cubic centimeters in volume), to form aplurality of predictably increasing outer diameters that increase to anouter diameter between 1.25 millimeters and 18 millimeters in diameter,by steps of between 0.2 millimeters and 0.4 millimeters increase indiameter. For instance, balloon 8810 may be inflated by selectedincreasing inflation volumes to cause the outer diameter to increase toa plurality of predictably increasing outer diameters that are equallyspaced increments in diameter between 0.2 millimeters and 0.4millimeters, such as to increase outer diameter by 0.25 millimeters foreach selected increasing inflation volume until balloon 8810 is inflatedto an outer diameter sufficient to occlude a blood vessel. It is alsoconsidered that balloon 8810 may be inflated with an inflation pressureof between 0.5 atmospheres and six atmospheres in pressure, such as toreach a sufficient outer diameter to occlude a blood vessel.Additionally, FIGS. 66A and B show balloon 8810 having third diameterBRD3 which may or may not be sufficient to occlude blood vessel 990 attreatment region 996.

FIG. 67A shows the cannula and balloon of FIG. 66A, with the ballooninflated to a selected fourth inflation volume. FIG. 67B is across-sectional view of apparatus 8800 of FIG. 67A from perspective “A”.Here, balloon 8810 is inflated to fourth inflation volume BRV4, fourthinflation pressure BRP4, fourth length BRL4, and fourth diameter BRD4.For example, FIGS. 67A and B show balloon 8810 inflated to a selectedincreasing fourth inflation volume BRV4 to form a predictably increasingfourth outer diameter BRD4 and to have a fourth inflation pressure BRP4that may be greater than first inflation pressure BRP1, second inflationpressure BRP2, or third inflation pressure BRP3 by less than fivepercent in pressure. Thus, balloon 8810 may be inflated to fourthinflation volume BRV4 sufficient to cause fourth inflation pressure BRP4to allow balloon 8810 to occlude blood vessel 990 at treatment region996, such as to occlude a flow or volume of fluid such as blood ortreatment agent from passing through blood vessel 990 past balloon 8810in directions 8860. According to some embodiments, fourth inflationvolume BRV4 may be a total inflation volume of gas or fluid up to 2.0cubic centimeters, such as a volume of between 0.03 cubic centimetersand 0.4 cubic centimeters (e.g., where inflation volume, such as fourthinflation volume BRV4 may be a total inflation volume of gas or fluidwithin balloon 8810, and does not include any gas or fluid withincannula 8802, or within a lumen, a tube, an inflation lumen, a catheter,a shaft, or other structure related to inflating balloon 8810 extendingwithin cannula 8802 or within balloon 8810).

In addition, fourth inflation pressure BRP4 may be an inflation pressureof between one atmosphere and six atmosphere in pressure, such as apressure between three atmosphere and four atmosphere, or between fouratmosphere and five atmosphere in pressure. Note, fourth inflationpressure BRP4 may be within five percent of any of inflation pressuresBRP1 through BRP3, thus any of inflation pressures BRP1 through BRP3 mayalso be between one atmosphere and six atmosphere in pressure, or may infact be equal to fourth inflation pressure BRP4. Further, according tosome embodiments, BRP3 or BRP4 may be a pressure sufficient to occludethe blood vessel without radially expanding the blood vesselappreciable, such as by expanding the blood vessel by less than five orten percent in outer diameter.

Also, according to some embodiments, balloon 8810 may include a propertysuch that when inflated to a first inflation volume (e.g., such as thirdinflation volume BRV3) balloon 8810 has a first inflated axial length(e.g., such as third length BRL3) and an outer diameter (e.g., such asthird diameter BRD3) of the balloon exerts a first inflation pressure(e.g., such as third inflation pressure BRP3) on an inner diameter of ablood vessel (e.g., such as blood vessel 990) sufficient to occlude theblood vessel at a treatment region (e.g., such as treatment region 996).Moreover, when inflated to a second greater inflation volume (e.g., suchas fourth inflation volume BRV4) balloon 8810 has a second inflatedaxial length (e.g., such as fourth length BRL4) that is sufficientlygreater than the first inflated axial length (e.g., such as third lengthBRL3) to allow the outer diameter of the balloon (e.g., fourth diameterBRD4) of the balloon to exert a second inflation pressure (e.g., such asfourth inflation pressure BRP4) on the inner diameter of the bloodvessel (e.g., such as blood vessel 990) that is less than appreciable,such as by being less than five percent greater than the first inflatedpressure (e.g., such as third inflation pressure BRP3). Specifically, asshown in FIGS. 67A and B, when balloon 8810 is inflated to fourthinflation volume BRV4, instead of growing to fifth inflation diameterBRD5, balloon 8810 is constrained by the inner diameter of blood vessel990 and only grows to fourth diameter BRD4 (e.g., where fourth diameterBRD4 is a diameter that may be within five or 10 percent of thirddiameter BRD3). Hence, for balloon 8810 to retain fourth inflationpressure BRP4 equal to or within five percent of third inflationpressure BRP3, instead of balloon 8810 growing in diameter to fifthdiameter BRD5, the balloon grows axially in length to fourth lengthBRL4, which is greater than third length BRL3, and which is greater thanfirst length BRL1 by BRLI1 plus BRLI2.

To design a balloon that limits fourth inflation pressure BRP4 asdescribed above consideration or selection of the following may be made:a deflated length of the balloon, a target inflated outer diameter ofthe balloon, the diameter and characteristics of the cannula, deflatedballoon diameter, balloon wall thickness, type of inflation gas orliquid, type of balloon material, diameters of the plurality ofpredictably increasing radial balloon outer diameters, volumes of theplurality of selected increasing balloon inflation volumes, innerdiameter of the blood vessel at the treatment region, blood or fluidflow pressure in the blood vessel proximate to the balloon, inflationpressure of the balloon during occlusion, actual outer diameter of theballoon in the blood vessel during occlusion, and other appropriateconsiderations such as those described herein.

For instance, first length BRL1 may be selected between eight and 10millimeters in length for a balloon to have a final radial outerdiameter of 3.25 millimeters (e.g., such as if fourth diameter BRD4 wereequal to 3.25 millimeters). Similarly, a first length BRL1 of betweenfive and six millimeters may be selected for a balloon to have a finalradial outer diameter of 4.25 millimeters (e.g., such as a fourthdiameter BRD4 of 4.25 millimeters). Also, in an embodiment, balloon 8810may have a preinflated outer diameter (e.g., such as first diameterBRD1) of between one millimeter and three millimeters in diameter, andinflated outer diameter (e.g., such as fourth diameter BRD4) of betweenfour millimeters and seven millimeters at an inflation pressure (e.g.,such as fourth inflation pressure BRP4) of between three atmosphere andfour atmosphere in pressure, while having an inflated axial length thatincreases with increasing inflation volume (e.g., such as third lengthBRL3 increasing to fourth length BRL4 with third inflation volume BRV3increasing to fourth inflation volume BRV4) to allow the balloon toocclude a blood vessel (e.g., such as blood vessel 990) while theballoon inflated outer diameter (e.g., such as fourth diameter BRD4)maintains an inflation pressure (e.g., such as fourth inflation pressureBRP4) of between three atmosphere and four atmosphere pressure on aninner diameter of the blood vessel (e.g., such as on an inner diameterof blood vessel 990 at treatment region 996).

Furthermore, balloon 8810 may be designed to inflate by selectincreasing inflation volumes to a total inflation volume which isgreater than, or oversized as compared to, an inner diameter of a bloodvessel, such as by being greater than an inner diameter of a bloodvessel by a selected diameter. Specifically, referring to FIGS. 67A andB, it is possible to inflate balloon 8810 to a plurality of selectedincreasing inflation volumes up to third volume BRV3 and then toincrease the inflation volume to fourth volume BRV4 to target fifthdiameter BRD5 which is greater than the inner diameter of blood vessel990 by oversized diameters 8870 plus 8872. For example, oversizeddiameters 8870 plus 8872 may add to be a diameter distance in a range ofbetween 0.1 millimeters and one millimeter in diameter distance, such asby totaling to be 0.25 millimeters in diameter.

Examples of balloon 8810 contemplated include a balloon having aninflated outer diameter (e.g., such as fourth diameter BRD4) of between1.25 millimeters and 12 millimeters in diameter (e.g., such as if fourthdiameter BRD4 were between four millimeters and seven millimeters indiameter), and an inflated length that increases in inflated length by atotal length of up to 15 millimeters (e.g., such as by increasing by atotal increased length of BRLI1 plus BRLI2). Specifically, in accordancewith embodiments, balloon 8810 may having an inflated length thatincreases in inflated length by a total length that is inverselyproportional to the preinflated length of the balloon. For instance, asshown in FIGS. 64A-67B, balloon 8810 may increase by a total increasedlength of BRLI1 plus BRLI2 of 0.5 mm for a balloon preinflated firstlength, BRL1 of eight mm (e.g., here, BRL4 is 8.5 mm), and increase by atotal increased length of BRLI1 plus BRLI2 of 0.25 mm for a balloonpreinflated first length, BRL1 of 10 mm (e.g., here, BRL4 is 10.25 mm)It is also contemplated that examples of balloon 8810 may have a wallthickness that decreases by between 10 percent and 75 percent inthickness, at an inflation pressure (e.g., such as fourth inflationpressure BRP4) of between three atmosphere and four atmosphere inpressure.

In a second example balloon 8810 may have first diameter BRD1 of 1.3millimeters at first inflation pressure BRP1 below one atmosphere inpressure, and fourth diameter BRD4 between four millimeters and sevenmillimeters at fourth inflation pressure BRP4 of between threeatmosphere and four atmosphere in pressure. Specifically, in this case,balloon 8810 may have an inner diameter of 0.044 inches and a wallthickness of 0.003 inches when deflated, such as when at first inflationvolume BRV1.

In another instance, balloon 8810 may have first diameter BRD1 of 1.3millimeters and be designed to expand to fifth diameter BRD5 of 14millimeters when inflated to fourth inflation pressure BRP4 of betweenone and six atmosphere in pressure, without balloon 8810 bursting orpermanently deforming. In other words, balloon 8810 may expand toseveral times its original diameter under low pressure (e.g., such asfourth inflation pressure BRP4 of less than six atmosphere in pressure)and then return to its original low profile dimension upon inflationvolume release (e.g., such as by returning to first diameter BRD1 uponreducing inflation volume from fourth inflation volume BRV4 to firstinflation volume BRV1). Thus, balloon 8810 may return to almost itsoriginal size upon or after deflation. For example, after inflation,balloon 8810 may return to an outer diameter that is within 10 percentof its preinflated diameter (e.g., such as within 10 percent of firstdiameter BRD1), an axial length within 10 percent of its preinflatedaxial length (e.g., such as within 10 percent of first length BRL1), anda wall thickness of within five percent of its preinflated wallthickness. Additionally, according to some embodiments, balloon 8810 mayinclude a property such that during deflation it forms a plurality ofdecreasing radial outer diameters, such as by forming radial outerdiameters third diameter BRD3, second diameter BRD2, and first diameterBRD1 during deflation from fourth inflation volume BRV4 back down tofirst inflation volume BRV1.

Furthermore, according to some embodiments, balloon 8810 may be made ofor include a balloon material having one or more of a block copolymer ofpolyether and polyester (e.g., such as a polyester sold under thetrademark Hytrel® of DUPONT COMPANY), a biocompatible polymer such as apolyether block amide resin (e.g., for instance, PEBAX® of ATOCHEMCORPORATION), a styrene isoprene styrene (SIS), styrene butadienestyrene (SBS), styrene ethylene butylene styrene (SEBS),polyetherurethane, ethyl propylene, ethylene vinyl acetate (EVA),ethylene methacrylic acid, ethylene methyl acrylate, and ethylene methylacrylate acrylic acid. It is also contemplated that balloon 8810 mayinclude a material from a material family of one of styrenic blockcopolymers and polyurethanes; or a melt processible polymer. Balloon8810 may also include a low durometer material, such as a material toallow the walls or outer diameter of balloon 8810 to gently occlude ablood vessel during infusion of therapeutic agents such as stem cells,genes, adenovirus, progenitor cells, and other treatment agents asdescribed herein.

It is to be appreciated that balloon 8810 may be formed by meltextruding a material, such as balloon material described above, into atube to form a balloon, and then bonding the balloon or tube to acannula, such as a catheter or cannula 8802. For example, a balloon ortube as described above can be bonded by laser, heat, shrink tube, oradhesive bonding to a catheter or cannula. Specifically, according tosome embodiments, a tube or balloon may be shrink tube bonded to cannula8802 such as at proximal attachment 8809 and distal attachment 8811 sothat exterior surface of balloon 8810 forms symmetrical shapes withrespect to an axis of cannula 8802 when balloon 8810 is inflated over arange of inflation volumes. For example, shrink tube bonding may be usedto bond balloon 8810 to cannula 8802 so that when the balloon isinflated from first inflation volume BRV1 to fourth inflation volumeBRV4, balloon 8810 forms a plurality of symmetrical shapes, such asfirst shape 8820, second shape 8822, third shape 8824, and fourth shape8826 during inflation. More particularly, such shrink tube bonding mayinclude an even or straight perpendicular radial bond of a balloon orballoon tube to a cannula with respect to an axis of the cannula toeffect a symmetrical inflation of the balloon over a range of selectedinflation volumes as mentioned herein. Hence, cannula 8802 may functionas one or more of a guide catheter, a delivery catheter, and a guidewirecatheter; while balloon 8810 may inflate to expand in size to an outerdiameter in a range of between one millimeter and 15 millimeters indiameter, such as to occlude a blood vessel injuring treatment infusionto a treatment region of the blood vessel.

According to some embodiments, a balloon high compliance balloon, suchas balloon 8810, may be heat bonded, laser bonded, shrink tube bonded,or attached with an adhesive to a cannula, such as cannula 8802 (e.g.,or cannula 9502 as shown in FIGS. 69A-70 and described in accompanyingtext, or a catheter as describe herein). Specifically, a balloon (e.g.,such as any balloon, occlusion device or filter device as describedherein) may be shrink tube bonded to a cannula so that the balloonexterior surface inflates to symmetrical shape with respect to an axisof the cannula. For instance, shrink tube bonding may provide and evenand straight bond of a balloon tube to a cannula with respect to an axisof the cannula to effect such symmetrical inflation of the balloon overa range of inflation volumes as mentioned herein.

Hence, a balloon may have a balloon outer diameter growth rate thatchanges in correlation to a percentage change in the inflation volume ofgas or fluid (e.g., such as fluoroscopy contrast media) within theballoon. For instance, it is possible to design a high complianceballoon formed of a material and by a process as described herein,having a length of between two millimeters and 20 millimeters, and adouble wall thickness between about 0.0003 inches and about 0.0038inches, such that an outer diameter of the balloon can inflate from onemillimeter when deflated to 18 millimeters when inflated withoutbursting or permanently deforming.

Specifically, a high compliance balloon formed of PEBAX 63D can bedesigned to have a deflated outer diameter and length to achieve agrowth rate greater than about 40% while maintaining an inflationpressure that increases by less than five percent. For instance, FIG. 68is a graph showing the relationship between the outer diameter of aballoon and the volume of inflation contrast fluid injected into theballoon. Here, FIG. 68 plots outer diameter of the balloon 8881 versusvolume of inflation contrast fluid injected into the balloon 8882 for a4.0 millimeter outer diameter by 10 millimeter long balloon of PEBAX 63Doperating at an inflation pressure below four atmospheres.

Note that although FIGS. 64A-68 show and the related discussiondescribes inflating balloon 8810 with selected inflation volumes toocclude a blood vessel, it can be appreciated that a balloon (e.g.,including balloon 8810) may be designed by a process or of the materialsdescribed herein and may have a dimension, characteristic, deflatedouter diameter, or deflated length, such that the outer diameter of theballoon may be inflation pressure controlled. More particularly, aballoon may be designed by a process or of the materials describedherein to have an outer diameter that can be controlled by controllingthe amount of inflation pressure of a gas (e.g., such as air, carbondioxide, or a gas having a fluoroscopy contrast agent) or a liquid(e.g., such as water, saline solution, or a fluid having a fluoroscopycontrast agent) used to inflate the balloon. Again, such a balloon maybe used as an occlusion device.

Hence, a balloon (e.g., such as balloon 8810) can be used with a cannulaor catheter (e.g., such as cannula 8802) that has a dimension suitablefor percutaneous advancement through a blood vessel to infuse atreatment agent (e.g., such as biological agents) into a treatmentregion, such as arterial vessels or venous vessels. For example, FIG.69A is a side perspective view of a cannula having a balloon attached toits distal end and an infusion lumen and accessory lumen running throughthe cannula. FIG. 69A shows apparatus 9500 having cannula 9502 withproximal end 9504 and distal end 9506. Cannula 9502 may be a cannula orcatheter such as a cannula similar to cannula 710 or any of the variousother guide, delivery, or guidewire catheters or cannulas describedherein. For instance, cannula 9502 may be include materials as describedabove for catheter 302 or 512, such asmay one or more of a synthetic ornatural latex or rubber, such as a polymer material; a polyetheramide; aplasticiser free thermoplastic elastomer; a thermoplastic blend; a blockcopolymer of polyether and polyester; a biocompatible polymer such as apolyether block amide resin; a polycarbonate or acrylonitrile bubadienestyrene (ABS); a bio-compatible polymer such as a polyether block amideresin; a styrene isoprene styrene (SIS), a styrene butadiene styrene(SBS), a styrene ethylene butylene styrene (SEBS), a polyetherurethane,an ethyl propylene, an ethylene vinyl acetate (EVA), an ethylenemethacrylic acid, an ethylene methyl acrylate, an ethylene methylacrylate acrylic acid, a material from a material family of one ofstyrenic block copolymers and polyurethanes, a melt processible polymer,a low durometer material, and nylon.

Balloon 9510 is axially connected to exterior surface 9508 of cannula9502 at proximal coupling 9509 and distal coupling 9511, at or adjacentdistal end 9506. Balloon 9510 may be a balloon, occlusion device, orfilter device such as balloon 2647, 3147, 3522, 3947, 2547, 3047, 3604,3704, 3804, 4004, 308, 2204, 2250, 2112, 314, 4520, 4620, 4820, 8810, orother balloons or occlusion devices. For example, balloon 9510 may be aballoon including a property such that when inflated to a selectedinflation volume the balloon will expand in size to an outer diametersufficient to occlude a blood vessel as described herein. In oneexample, balloon 9510 may be a high-compliance balloon made of a lowdurometer material or it may function similarly to balloon 8810 asdescribed herein.

In addition, cannula 9502 may have infusion lumen 9520 extending fromproximal end 9504 to distal end 9506 and exiting infusion opening 9522distal to balloon 9510. Furthermore, cannula 9502 may also includeaccessory lumen 9530 extending from proximal end 9504 to distal end 9506and exiting accessory opening 9532 distal to balloon 9510.

Thus, according to some embodiments, infusion lumen 9520 or accessorylumen 9530 may be adapted to have a guidewire, such as guidewire 9533disposed therethrough to guide cannula 9502 through a blood vessel(e.g., such as blood vessel 990) to a treatment region (e.g., such astreatment region 996). For instance, infusion lumen 9520 or accessorylumen 9530 may be adapted to have a guidewire disposed therethrough toguide cannula 9502 to a location in a blood vessel with respect todelivery catheter 310 as shown and described with respect to FIG. 3,cannula 720 as shown and described with respect to FIGS. 7-19, orcannula 9902-9904 as shown and described with respect to FIGS. 86-89.More particularly cannula 9502 may have a dimension or profilecompatible with or suitable to be received within, or be slidablydisposed within a guide catheter (e.g., such as a guide catheter orcannula as described herein, including guide catheter 302) having anouter diameter in a range of between 5 French and 9 French. It is alsocontemplated that cannula 9502 may have a dimension suitable forpercutaneous advancement through a blood vessel such as blood vessel990.

FIG. 69B is a cross section view of first section 9556 of apparatus 9500of FIG. 69A from perspective “A”. FIG. 69B shows cannula 9502 havingouter diameter COD1 less than 0.09 inches. It is also contemplated thatcannula 9502 may include a shaft having an outer diameter which is lessthan 0.06 inches in diameter. FIG. 69B also shows accessory lumen 9530having inner diameter ALID1 and infusion lumen 9520 having innerdiameter ILID1. According to some embodiments inner diameter ALID1 maybe less than inner diameter ILID1. In addition, it is contemplated thatinfusion lumen 9520 may have inner diameter ILID1 greater than 0.01inches in diameter.

Also, accessory lumen 9530 may have an inner diameter that is greaterthan between 0.01 inches and 0.5 inches in diameter, such as an innerdiameter capable of accommodating a guidewire having a diameter of atleast 0.01 inches. Furthermore, lumen 9530 may be used to infuse atreatment agent to a treatment region, or to aspirate fluids from atreatment region (e.g., see hole 988 of FIG. 9 and accompanying text).

It is also contemplated that accessory lumen 9530 may have a dimensionsuitable to allow for several usages including continuous guidewireaccess during an infusion process to maintain the location of cannula9502, to monitor pressure distal to balloon 9510, to allow foraccessibility of other accessories to a location distal to balloon 9510.For example, accessory lumen 9530 may allow for accessibility of a flowand pressure wire to measure distal flow and pressure, or other types ofsensor wires to make measurements in a location of a blood vessel distalto balloon 9510. Specifically, accessory lumen 9530 may have a dimensionsuitable to allow a device to be connected to a proximal end of theaccessory lumen, such as at proximal access lumen port 9554, or for adevice to be disposed through accessory lumen 9530 to measure one ofchronic renal failure (CRF), electrocardiogram (EKG), oxygen level,pressure, flow, blood sampling, or temperature, such as at treatmentregion 996. Moreover, it is contemplated that accessory lumen 9530 maybe used to measure or to receive a device to measure various otherphysiological parameters, such as at treatment region 996 distal toballoon 9510.

According to some embodiments infusion lumen 9520 or accessory lumen9530 may each include a surrounding material, sleeve, cannula or lumen,such as by being constructed with composite tube. For example, thecomposite tube may include a braid or coil reinforced polyamide orpolymer tube. Thus, infusion lumen 9520 or accessory lumen 9530 mayinclude a reinforced tube, to prevent catheter or lumen (e.g., such aslumen 9502) kinking. Note, that composite accessory or infusion lumensuch as described above with respect to balloon section 9511, thirdsection 9558 and fourth section 9559 also help maintain lumen roundness.

Infusion lumen 9520 or accessory lumen 9530 may be adapted to receive aguidewire or have a guidewire disposed therein and exiting a proximalopening at proximal end 9506 (e.g., such as opening 9532 or opening9522), so that cannula 9502 can be used in an over-the-wire fashion, orhave the guidewire removed therefrom. It is also considered thatinfusion lumen 9520 or accessory lumen 9530 may have a proximal opening,such as port 9554 or 9552 located proximal to balloon 9510 and within 35centimeters of the distal end of cannula 9502 such that cannula 9502 canbe used in rapid exchange fashion.

FIG. 69C is a cross sectional view of second section 9557 of apparatus9500 of FIG. 69A from perspective “B”. FIG. 69C shows second section9557 of cannula 9502 having width CW1 between 0.03 inches and 0.05inches, such as a width of 0.04 inches. FIG. 69C also shows cannula 9502having height CHI between 0.04 inches and 0.06 inches, such as a heightof 0.055 inches.

FIG. 69D is a cross sectional view of balloon section 9511 of FIG. 69Afrom perspective “C”. FIG. 69D shows balloon 9510 including a propertysuch that when inflated to inflation volume BIV1, such as a selectedinflation volume, the balloon will expand in size to outer diameter BOD1sufficient to occlude a blood vessel. For example, balloon 9510 mayinclude a property such that the balloon has inflation pressure BPI1 ofless than five atmospheres in pressure at inflation volume BIV1.

Moreover, according to some embodiments balloon 9510 may have a propertysuch that when inflated to a plurality of increasing inflation volumes,the balloon forms a plurality of increasing radial outer diameters, andhas an inflation pressure that increases by less than five percent inpressure over the range of the increasing inflation volumes. Forexample, FIG. 70 is a cross sectional view of the balloon section ofFIG. 69A from perspective “C”, with the balloon inflated to a secondvolume that is less than that shown in FIG. 69D. FIG. 70 shows balloonsection 9511 after balloon 9510 inflated with inflation volume BIV2which is less than volume BIV1 to form radial outer diameter BOD2 whichis less than BOD1. Thus, although the inflation volume of balloon 9510can be increased from inflation volume BIV2 to BIV1, the inflationpressure of balloon 9510 may increase from pressure BPI2 to pressureBPI1, where pressure BPI1 is less than 105% of BPI2 in pressure. Forexample, balloon 9510 may be a balloon that expands in size to an outerdiameter, such as diameter BOD1, in a range of between one millimeterand 15 millimeters in diameter, controlled by volume injection, such asto inject volumes BIV2 and BIV1 of a gas or a fluid.

Cannula 9502 may further include balloon inflation lumen 9540 extendingfrom proximal end 9504 to balloon 9510 and exiting and inflation opening(not shown) within balloon 9510. Balloon inflation lumen 9540 and theinflation opening may have a diameter sufficient to inflate and deflateballoon 9510 as described herein, such as by having a diameter ofbetween 0.01 inches and 0.02 inches in diameter. Also, infusion lumen9520 may have an inner diameter that is at least 0.015 inches indiameter. In addition, balloon inflation lumen 9540 may be connected toan inflation device or syringe to inflate balloon 9510 as describedherein.

It is also to be appreciated that cannula 9502 may include additionalcannula or lumen extending through cannula 9502, such as from proximalend 9504 to distal end 9506, or otherwise as described herein. Moreover,according to some embodiments, each of infusion lumen 9520, accessorylumen 9530, inflation lumen 9540, or other lumen described herein mayinclude or have its own sleeving, cannula, or other surrounding materialor structure having a dimension to fit within the surrounding cannula inwhich the lumen is disposed or extending through. For example, each ofinfusion lumen 9520, accessory lumen 9530, and inflation lumen 9540 mayinclude an independent sleeve of material extending through cannula 9502(e.g., such as by fitting within cannula 9502 and restricted to thedimension of cannula 9502 as described herein) and function with thatsleeving.

In addition, as shown in FIG. 69A, accessory lumen 9530 may extend firstlength LL1, infusion lumen 9520 may extend second length LL2 andinflation lumen may extend third length LL3 in distance beyond or out ofproximal end 9504, where at least one of the first length LL1, secondlength LL2, or third length LL3 is a different distance in length thanat least one of the others. Also, it is to be appreciated that accessorylumen 9530 being of a dimension suitable to infuse a first volume oftreatment agent to a treatment region (e.g., such as treatment region996) and to ask for a second volume of blood and treatment agent fromthe treatment region. Similarly balloon inflation lumen 9540 may have adimension suitable to inflate balloon 9510 with a volume of (e.g., suchas volume BIV1) a gas or liquid to an inflation pressure (such asinflation pressure BPI1) of less than 6 atmospheres and maintain theinflation volume or inflation pressure for at least 4 minutes.

As shown in FIG. 69A cannula 9502 may have luer adaptor 9550 at orattached to proximal end 9504. Thus, accessory lumen 9530, infusionlumen 9520, or inflation lumen 9540 may extend through luer adaptor 9550or be attached to luer adaptor 9550 at proximal end 9504. It is alsoconsidered that luer adaptor 9550 may include proximal end of accesslumen 9534, proximal end of inflation lumen 9544, or proximal end ofinfusion lumen 9524. Correspondingly, proximal end of access lumen 9534may end with proximal access lumen port 9554, proximal end of inflationlumen 9544 may end with balloon inflation port 9553. Luer adaptor 9550may include a port, such as proximal access lumen, port 9554 to connectto a hemastatic valve. Furthermore, proximal end of inflation lumen 9524may end with proximal infusion port 9552, such as a port having a springloaded pressure seal. Also, balloon inflation port 9553 may be a port tohave an inflation device or syringe attached thereto as describedherein. Some embodiments of inflation device or syringes contemplatedfor use with apparatus 9500 are discussed herein with respect toapparatus 9700 and 9800 of FIGS. 75A-81. For instance, an inflationdevice or syringe attached to balloon inflation port 9553 may include alabel on its surface such as to identify a purpose or informationrelated to the device or syringe.

According to some embodiments luer adaptor may have a dimension suitableto allow a first volume of treatment agent to be infused to a treatmentregion, to allow a second volume of blood and treatment agent to beaspirated from the treatment region (e.g., see hole 988 of FIG. 9 andaccompanying text), and to allow a volume of a gas or fluid to inflateballoon 9510 to a pressure, such as BPI1, of less than six atmospheres,and to maintain the inflation volume (e.g., such as BVI1) for at leastfour minutes.

FIG. 69E is a cross sectional view of third section 9558 of FIG. 69Afrom perspective “D”. FIG. 69E shows third section 9558 of cannula 9502having second width CW2 of between 0.035 inches and 0.055 inches, suchas having a width of 0.048 inches. FIG. 69E also shows cannula 9502having a second height CH2 of between 0.05 and 0.065 inches, such as aheight of 0.057 inches. For instance, according to some embodiments,third section 9558 may be a section that extends from a proximal end ofballoon 9510 to a distal end of balloon 9510, such as a balloon shaft.More particularly, third section 9558 may include balloon section 9511,and may have a profile that is taller or wider than second section 9557,such as a profile shown in FIG. 69E resulting from third section 9558including balloon 9510.

FIG. 69F is a cross section view of fourth section 9559 of FIG. 69A fromperspective “E”. FIG. 69F shows fourth section 9559 having third widthCW3 of between 0.03 inches and 0.045 inches, such as having a width of0.037 inches. FIG. 69F also shows fourth section 9559 having thirdheight CH3 of between 0.05 inches and 0.065 inches such as having aheight of 0.057 inches. According to some embodiments, balloon inflationlumen 9540 does not extend into either third section 9558 or fourthsection 9559.

For example, the distal end of cannula 9502 may have a soft tip having aplurality of compliant tubes, lumen, sub-cannula with extended portionsextending past the distal end of the cannula, where the extendedportions are bound together by a compliant material wrap. Specifically,for example, as shown in fourth section 9559 of FIGS. 69A and 69F,infusion lumen 9520 or accessory lumen 9530 may be joined to or joinedby a soft tube made with a polymer material that is bondable to theinfusion or accessory lumen tube. Moreover, the polymer may have a lowerhardness Durometer than either the tube of infusion lumen 9520 or thetube of accessory lumen 9530. In addition, the soft section describedabove may be further wrapped with another soft jacket wrapping over thesoft tubes to form the tip of cannula 9502. It is contemplated that allthe joining and wrapping described above may be performed with laserbonding, heat melting, or adhesive gluing.

Also, according to some embodiments, cannula 9502 may have supportmandrel 9560 disposed within the cannula and exiting or ending atproximal end 9504 and extending proximal to, within the length of, ordistal to balloon 9510. Specifically, mandrel 9560 may extend to balloon9510 such as shown by balloon section 9511 and may or may not extendpast balloon 9510, such as shown by third cross section 958. Thus,mandrel 9560 may extend through third section 9558 to support apparatus9500 through the third section, where exterior surface 9508 or cannula9502 may not exist through the third section. It is also contemplatedthat support mandrel 9560 may have a partial length, such as beginningat proximal end 9504 or beginning distal to proximal end 9504 andextending to the midpoint between proximal end 9504 and distal end 9506,a point along first section 9556, or a point along second section 9557.In addition, as a marker band, shrink wrap, infused material, extrudedmaterial, laser-bonded material, heat-bonded material, or other materialor wrap may be used to couple, attach, or connect mandrel 9560,accessory lumen 9530, or infusion lumen 9520 within balloon section9511. For example, as described below, a radio-opaque marker band,material infused from third section 9558, or material that is includedin third section 9558 may extend through a portion or all of balloonsection 9511 to connect together or be a part of inflation lumen 9540,accessory lumen 9530, infusion lumen 9520, or support mandrel 9560.

It is also considered that where materials described above with respectto third section 9558 extend into balloon section 9511, materialsincluded in or used to form fourth section 9559 may also exist or formcomponents of the structure within balloon section 9511 or third section9558 as described herein.

Moreover, according to some embodiments, mandrel 9560 may have variouscross-sectional shapes, such as a circle, oval, square, rectangle, orother polygon or curved cross-sectional shape as mandrel 9560 extendsthrough cannula 9502. For example, mandrel 9560 may have outer diameterMOD1 which is constant, or which reduces with extension of the mandrelfrom proximal end 9504 toward distal end 9506. For example, mandrel 9560may have a constant outer diameter MOD1 of less than 0.017 inches indiameter. Alternately, mandrel 9560 may have proximal outer diameterMOD1 that begins with less than 0.017 inches at proximal end 9504 andsteps down to a plurality of lesser outer diameters that end with adistal diameter of the MOD2 between 0.012 inches and 0.003 inches indiameter such as shown in FIG. 70.

In addition, it is contemplated that support mandrel 9560 may beanchored or attached to a proximal adaptor such as luer adaptor 9550,cannula 9502 at proximal end 9504, as well as cannula 9502 within thelength of balloon 9510, such as where the balloon is connected to theexterior surface of the cannula. It is also contemplated that supportmandrel 9510 may only be attached at one or none of the locationsidentified above.

Support mandrel 9560 may be used to add stiffness to or reinforcecatheter 9520, such as to prevent the catheter from kinking. Supportmandrel 9560 may include one or more of titanium, nickel-titanium(NiTi), stainless steel, a plastic, a polymer, a polyether block amideresin having a durometer hardness of about 50 to about 70 shore D, apolyimide, a polyethylene, or other suitable materials or metals, suchas those having a sufficient stiffness to prevent the cannula fromkinking. For example, support mandrel 9560 may extend from proximal end9504 to a location distal to proximal coupling 9517 to prevent or reducethe possibility of cannula 9502 from kinking when the cannula is notsupported by a guidewire, such as is a guidewire used during insertionof cannula 9502 is removed from accessory lumen 9530 and accessory lumen9530 is used to monitor parameters at a treatment region.

Note that material coupling infusion lumen 9520, accessory lumen 9530,mandrel 9560, or inflation lumen 9540 in balloon section 9511 may alsobe coupled to or may include cannula 9502, such as in embodiments wherecannula 9502 extends through balloon section 9511. It may be appreciatedthat one or more marker bands, polymer sheaths, on other materials maybe mounted around all tubes, mandrel, lumens, or cannula running throughballoon 9510, or can be mounted over single components thereof. Thus, ifa marker band is mounted over a single component, a polymer sheath maybe added to bundle together more than one of the components identifiedabove, such as within the length of balloon 9510. Specifically, apolymer sheath may bundle together cannula 9502, inflation lumen 9540,mandrel 9560, or accessory lumen 9530 at a point along the length ofballoon 9510 (e.g., such as where balloon 9510 is coupled to exteriorsurface 9508). According to an embodiment, balloon inflation lumen 9540may extend through exterior surface 9508 and to balloon 9510, and markerband 9570 may be attached to cannula 9502 at the location that ballooninflation lumen 9540 exits to balloon 9510 at an inflation opening.Thus, placement of marker band 9570 may assist in bonding of ballooninflation lumen 9540 to cannula 9502, may create a more resilient bond,and may protect the inflation opening.

According to some embodiments, apparatus 9500 may include at least oneradio-opaque marker band. For example, FIGS. 69A, 69D, and 70 showradio-opaque marker band 9570 around the exterior of accessory lumen9530, infusion lumen 9520, and mandrel 9560 at midpoint 9516 of balloon9510. Moreover, as described above, marker band 9570 may encircle aportion of balloon section 9511 that includes material infused therefrom or also included in third section 9558. In addition, it is to beappreciated that marker band 9570 may be around the exterior of cannula9502 (e.g., if cannula 9502 extends through balloon section 9511),accessory lumen 9530, or infusion lumen 9520 at midpoint 9516 of theballoon, proximal end 9517 of the balloon or distal end 9518 of theballoon (e.g., proximal end 9517 and distal end 9518 may correspond tothe “shoulder” where the balloon is coupled to the exterior surface ofthe cannula). Note that more than one marker band may be used such as atmore than one of the locations identified above.

According to some embodiments, lengths, diameters, materials, and othercharacteristics of cannula 9502, infusion lumen 9520, accessory lumen9530, inflation lumen 9540, mandrel 9560, balloon 9510, or othercomponents mentioned with respect to FIGS. 69A-F and 70 may be selectedso that apparatus 9500 may assist in or be used for treatment agent orcell infusion to treat acute myocardia infraction (AMI) or other formsof loss of heart function due to heart muscle damage.

Another example of a cannula or catheter that has a dimension suitablefor percutaneous advancement through a blood vessel to infuse atreatment agent (e.g., such as biological agents) into a treatmentregion, such as arterial vessels or venous vessels is a cannula havingcoaxial or co-linear lumen extending therethrough. For example, FIG. 71Ais a cross-sectional view of a cannula and a balloon, where the cannulaincludes coaxially aligned lumens. As shown in FIG. 71A, apparatus 9100has cannula 9102 having proximal end 9104 and distal end 9106 andballoon 9110 axially coupled to the exterior surface of the cannula ator adjacent distal end 9106, where balloon 9110 includes a property suchthat when inflated, the balloon may expand in size to an outer diametersufficient to occlude a blood vessel. FIG. 71B is a cross-sectional viewof apparatus 9100 of FIG. 71A from perspective “A”. Cannula 9102includes guidewire tube 9132 extending from proximal end 9104 to distalend 9106 and existing guidewire opening 9133. Guidewire tube 9132 ispart of or includes guidewire lumen 9130.

Infusion tube 9122 is disposed around guidewire tube 9132 and extendsfrom proximal end 9104 to distal end 9106 and exist infusion opening9123. Also shown, infusion tube 9122 includes infusion lumen 9120. FIGS.71A and B also show inflation lumen 9140 defined between infusion tube9122 and cannula 9102. According to some embodiments, guidewire tube9132, infusion tube 9122, and inflation lumen 9140 are coaxially alignedwith an axis of cannula 9102 (e.g., such as shown in FIGS. 71A and B).

It is to be appreciated that inflation lumen 9140 extends to balloon9110 and has a dimension suitable to inflate balloon 9110. Similarly,infusion tube 9122 has an outer diameter sufficient to infuse atreatment agent, such as treatment agents described herein, to atreatment region distal to balloon 9110. Next, guidewire tube 9132 has asufficient outer diameter and be adapted to have a guidewire disposedtherethrough to guide cannula 9102 through a blood vessel to a treatmentregion, such with respect to guiding cannula or catheters (e.g., such ascannula 9502) to a treatment region of a blood vessel.

As shown in FIG. 71B, cannula 9102 may have an exterior surface thatforms a circular cross-section with respect to perspective “A” whereballoon 9110 is axially coupled to the exterior surface of cannula 9102.Sealing on a round shaft allows for a more concentric balloon outerdiameter profiles, such as elastomeric balloon inflation profiles. Aconcentrically inflated balloon profile puts can put an even stress orinflation pressure on the balloon wall to seal around or occlude a bloodvessel more reliably and evenly. Similarly, it is contemplated thatinfusion tube 9122 may be coupled or attached to the exterior surface ofguidewire tube 9132 at a location or along locations distal to balloon9110, such as adjacent to or at the distal end of cannula 9102.

FIG. 72A is a cross-sectional view of a cannula and a balloon, where thecannula includes coaxially and co-linearly aligned lumens. As shown inFIG. 72A, apparatus 9200 has cannula 9202 having proximal end 9204 anddistal end 9206 and balloon 9210 axially coupled to the exterior surfaceof the cannula at or adjacent distal end 9206, where balloon 9210includes a property such that when inflated, the balloon may expand insize to an outer diameter sufficient to occlude a blood vessel. FIG. 72Bis a cross-sectional view of apparatus 9200 of FIG. 72A from perspective“B”. Cannula 9202 includes guidewire tube 9232 extending from proximalend 9204 to distal end 9206 and existing guidewire opening 9233.Guidewire tube 9232 is part of or includes guidewire lumen 9230.

FIGS. 72A and B also show infusion lumen 9220 defined between guidewiretube 9232 and cannula 9202. According to some embodiments, guidewiretube 9232 and infusion lumen 9220 are coaxially aligned with an axis ofcannula 9202, such as shown in FIGS. 72A and B. Inflation tube 9240 isshown extending from proximal end 9204 to balloon 9210 and isco-linearly aligned with an axis of cannula 9202. It is contemplatedthat inflation tube 9240 may be attached or coupled to cannula 9202 suchas by adhesive, heat bonding, or laser bonding. Thus, guidewire lumen9330, guidewire tube 9332, and inflation lumen 9340 may be co-linearlyaligned with an axis of cannula 9302.

It is to be appreciated that inflation tube 9240 extends to balloon 9210and has a dimension suitable to inflate balloon 9210. Similarly,infusion lumen 9220 has an outer diameter sufficient to infuse atreatment agent, such as treatment agents described herein, to atreatment region distal to balloon 9210. Next, guidewire tube 9232 has asufficient outer diameter and be adapted to have a guidewire disposedtherethrough to guide cannula 9202 through a blood vessel to a treatmentregion, such with respect to guiding cannula or catheters to a treatmentregion of a blood vessel.

It is also contemplated that cannula 9202 may have an exterior surfacethat forms a circular cross-section with respect to perspective “A”where balloon 9210 is axially coupled to the exterior surface of cannula9202. Similarly, it is contemplated that infusion tube 9222 may becoupled or attached to the exterior surface of guidewire tube 9232 at alocation or along locations distal to balloon 9210, such as adjacent toor at the distal end of cannula 9202.

FIG. 73 is a cross-sectional view of a cannula and a balloon, where thecannula has coaxially and co-linearly aligned lumens. FIG. 73 showsapparatus 9300 having cannula 9302. Cannula 9302 includes guidewire tube9332 forming guidewire lumen 9330 is coaxially aligned with infusionlumen 9320. FIG. 73 also shows inflation lumen 9340 formed withincannula 9302, and balloon 9310 axially coupled to the exterior surfaceof cannula 9302. Balloon 9310 may be a part of or correspond to aballoon such as described above with respect to balloon 9110. Similarly,infusion lumen 9320, guidewire tube 9332, guidewire lumen 9330, andcannula 9301 may have an outer diameter, dimension, or character tofunction similarly to their counterparts described above with respect toFIGS. 71A and B.

Moreover, according to some embodiments, none, any, or all of guidewiretube 9132, infusion tube 9122, inflation lumen 9140, guidewire tube9232, infusion lumen 9220, inflation tube 9240, guidewire tube 9332,infusion lumen 9320, or inflation lumen 9340 may include or have its ownsleeving, cannula, or other surrounding material or structure having adimension to fit within the surrounding cannula in which the lumen isdisposed or extending through, such with respect to lumen 9520 at FIGS.69A-F.

Additionally, because of it's structure, apparatus 9100, 9200, and 9300may track better in tortuous vasculature than cannula or catheters thatdo not have lumen coaxially or co-linearly located. In addition, acoaxial or co-linearly constructed catheters can be easier to fabricate.For instance, various processes may be used to form apparatus 9100,9200, or 9300 of FIGS. 71A-73. For example, one or more materials may bemelt-extruded to form a multi-lumen extruded cannula having a pluralityof coaxially aligned tubes with respect to an axis of the cannula, whereeach coaxially aligned tube has an exterior surface with a circularcross-sectional shape with respect to the axis of the cannula. Then, aballoon may be axially sealed to the circular cross-sectional exteriorsurface of the cannula where the balloon includes a property such thatwhen inflated, the balloon with expand in size to an outer diametersufficient to occlude a blood vessel (e.g., such as described above withrespect to balloon 9110).

A process for forming apparatus 9100, 9200, or 9300 of FIGS. 71A-73, asdescribed above may also include melt-extruding at least one material toform a number of tubes where some of the tubes may be inserted intoother tubes to form a multi-tube cannula having a number of coaxiallyaligned tubes or co-linearly aligned tubes with respect to an axis ofthe cannula, where each of the tubes has a circular cross-sectionalshape with respect to an axis of the cannula. Then, a balloon (e.g., asdescribed for balloon 9110) may be axially sealed to the circularcross-sectional exterior surface of the cannula.

Next, a process for forming apparatuses 9100, 9200, or 9300 of FIGS.71A-73, as described above might include placing a mandrel having acrescent-shaped cross-section within an infusion tube, placing aninflation tube on a support mandrel next to the infusion tube, wrappingthe infusion tube and the inflation tube in a jacket material, insertingthe jacket material into a shrink tube, and heating the shrink tubesufficiently to melt a portion of the infusion tube and the inflationtube material so that those materials are redistributed to form acannula having the infusion tube and inflation tube coaxially alignedwith respect to an axis of the cannula.

It is also considered that a process for forming apparatus 9100, 9200,or 9300 of FIGS. 71A-73, as described above might include placing around support mandrel within a portion of a guidewire tube and placingthe guidewire tube within an infusion tube so the guidewire tube iscoaxially aligned with the infusion tube. Note that it can beappreciated the guidewire tube and infusion tube may each have acircular cross-section with respect to an axis of the infusion tube.Next, two crescent-shaped mandrel may be placed between the guidewiretube and the infusion tube at or along a location where the supportmandrel is within the guidewire tube. The two crescent-shaped mandrelmay be located at opposing axial locations to form a construction. Theconstruction described above then may be inserted into a shrink tube andheated (e.g., such as by thermal heat or laser energy) sufficiently tomelt the infusion tube to a portion of the guidewire tube, to form oneor more tack joints where the crescent mandrels do not support theinfusion tube, and thus the infusion tube bonds to the guidewire tube.

For example, FIG. 74A is a cross-sectional view of the apparatus of FIG.71A from perspective “C” before forming tack joints between theguidewire tube and the infusion tube. FIG. 74A shows the structure ofapparatus 9100 having guidewire opening 9133 within guidewire tube 9132and infusion tube 9122 around infusion opening 9123 and guidewire tube9132. FIG. 74B is the structure of FIG. 74A after forming tack jointsbetween the guidewire tube and the infusion tube. For instance, FIG. 74Bis the structure shown of apparatus 9100 after tack joints 9470 and 9472are formed such as by heat or laser energy as described above withrespect to forming apparatus 9100, 9200, and 9300 of FIGS. 71A-73. Thus,after tack joints 9470 and 9472 are formed, FIG. 74B shows infusionopenings 9423 formed between attached infusion tube sections 9420 and9422, and guidewire tube 9132. Note that the structures and processesdescribed above with respect to FIGS. 74A and B, such as forming tackjoints, may also be applied to apparatus 9200 and 9300 of FIGS. 72A-73.Furthermore, the structure and processes described above with respect toFIGS. 72A-73 may also be applied to apparatus 9100 of FIGS. 71A and B.

Some embodiments of inflation device or syringes contemplated for usewith apparatus, cannula, and catheters, described herein (e.g.,including apparatus 9100, 9200, 9300, 9500 of FIGS. 69A-74) forinflating or deflating balloons described herein (e.g., such as balloon8810 and 9510 of FIGS. 64A-70) may include one or more inflationsyringes. For example, FIG. 75A is a cross sectional view of anapparatus to inflate a low volume balloon to occlude a blood vessel. Forexample, apparatus 9700, as will be shown and described below in FIGS.75A-80 may be used to inflate a balloon coupled to a distal end of acannula having an inflation lumen extending from the balloon through acannula and out a proximal exit in the cannula where the lumen will becoupled to apparatus 9700. FIG. 75A shows apparatus 9700 having largevolume syringe 9720 and low volume syringe 9750 within an elongatedhollow inner diameter of the plunger of large volume syringe 9720. FIG.75B is a cross-sectional view of the apparatus of FIG. 75A fromperspective “A”.

Large volume syringe 9720 is shown having barrel 9702 which forms anelongated hollow body proximal end 9704, and distal end 9706. Barrel9702 of apparatus 9700 is shown cut away in the travel region of theouter plunger 9703. Outer plunger 9703 incorporates one or more seals onpiston 9707, which do not allow fluid/air flow between the outerdiameter (OD) of the outer plunger 9703 and the inner diameter (ID) ofbarrel 9702 in the area where they form a seal. The lumen/ID of thebarrel 9702 is in communication with the output extension tube 9714 andpressure gage 9705, such that as outer plunger 9703 is translateddistally, fluid may be expelled out of the extension tube 9714 and thepressure applied to the fluid may be measured. The distal end ofextension tube 9714 is terminated in a male Luer Lock connector 9716.Thus, large volume syringe 9720 has an opening in the distal end tocouple to a proximal exit of a cannula, such as by coupling male LuerLock connector 9716 to a lumen in a cannula. More particularly,embodiments of apparatus 9700 and 9800 may attach to delivery catheter2620 or catheter system 3000, such as by coupling male Luer Lockconnector 9716 to fitting 2640 as shown in FIGS. 26-29 or fitting 3040as shown in FIG. 30.

The position of the outer plunger 9703 in the barrel 9702 may be lockedinto position or unlocked to move freely by actuating outer plunger lock9708. Outer plunger lock 9708 is on the proximal end of the barrel 9702and can have many configurations. The simplest configuration is apressure/force engagement of the proximal portion of plunger 9703 withsufficient force and material coefficient of friction to hold plunger9703 in place when the lock 9708 is engaged. For example, the basicmechanism can be the similar to lock/unlock mechanisms for use onballoon inflation devices, indeflators and syringes.

According to some embodiments, outer plunger 9703 is longitudinallyslidable within barrel 9702 and has a first shaft with first piston 9707disposed on the first shaft distal end. In accordance with embodiments,first piston 9707 and the shaft have elongated hollow inner diameter9740 with inner plunger 9709 longitudinally slidable within the innerdiameter. Inner plunger 9740 has a second shaft with second piston 9710disposed on the second shaft distal end. Therefore, the inner diameterand second plunger define low volume syringe 9750 having a volumerelatively substantially less than a volume of large volume syringe9720.

For example, low volume syringe 9750 is may communicate with the drawvolume of internal volume of large volume syringe 9720 in barrel 9702distal to plunger 9707. For example, outer plunger 9703 is a hollowconstruction in which inner plunger 9709 resides. Inner plunger 9709 maycontain seals 9710 which perform the same function for the inner plunger9709 and the ID of the outer plunger 9703 as seals 9707 do for the outerplunger 9703 and the ID of the barrel 9702. In its most distal travelposition, the distal end of the inner plunger 9709 aligns with or isvery close to the distal end of the outer plunger 9703. If the distalposition of the inner plunger 9709 is too far proximal of the distal endof the outer plunger 9703, then it is possible that air could gettrapped in the ID of the outer plunger 9703 that is distal to the distalend of the inner plunger 9709. As previously explained, trapped air isnot desirable and should be avoided in these applications. In onedesign, the ID of the barrel 9702 is designed such that it canaccommodate a significant protrusion of the inner plunger 9709 distal tothe distal end of the outer plunger 9703 and distal to the seals 9710.

Also, apparatus 9700 may include one or more lock mechanisms to lock theplunger of each syringe so that a user can selects whether the plungeris free or constrained to move in response to the rotation of itsthreads or a lock can be used to engage the plunger surface(s) withsufficient friction to prevent accidental plunger motion (in this casethe threads aren't really needed to provide the mechanical advantage tomore easily produce high pressures, since the pressures are to be low),the plunger handle configuration modified to make accidental motion lesslikely (i.e. from a “T” shape to a more round shape). As shown in FIG.75A, low volume syringe 9750 may have its own associated translation andlocking control. Specifically, large volume syringe 9720 may use outerplunger lock 9708 to releasably secure plunger 9703 to lock piston 9707at various locations along barrel 9702. Correspondingly, low volumesyringe 9750 may use inner plunger lock 9711 to releasably secureplunger 9709 to lock piston 9710 at various locations along innerdiameter 9740. Thus, inner plunger lock 9711 is on the proximal end ofthe outer plunger 9703 and allows the locking and unlocking of the innerplunger 9709 position relative to the outer plunger 9703. Inner plungerlock 9711 may have a mechanism similar to that of the outer plunger lock9708.

The maximum proximal travel position of the inner plunger is constrainedto limit the amount of fluid that may be drawn into the ID of outerplunger 9703 (or alternatively or in addition to limit the minimumprotrusion of the distal end of the inner plunger 9709 into the ID ofbarrel 9702). Many mechanisms are commonly used to accomplish this, themost common utilize OD or cross-section changes of the plunger 9709 (orthe ID of the outer plunger 9703) to interfere with portions of thedevice that it must translate through, such as the lock 9711. (A similarmethod may be used to constrain the proximal travel of the outer plunger9703.) The limiting of plunger 9703 or 9709 travel sets the fluiddisplacement allowed for that plunger. In a design for a compliantballoon, the displacement set for inner plunger 9709 is the maximumincremental injection that can be safely injected into the catheter toincrementally inflate the balloon or less. This is an important safetyfeature.

In addition, according to some embodiments, the proximal end of theouter plunger 9703 may contain a mechanism to allow the selection ofdifferent proximal travels of inner plunger 9709 and, thus allow asingle inflation/deflation device to safely operate catheters withdifferent inflation or deflation volumes. Alternately or in addition,the previously mentioned proximal travel limit (used to initially limitthe inflation of a compliant balloon) may be removed (a distal limit maybe added) and the inner plunger 9709 may subsequently be used to morerapidly inflate and deflate the balloon. Alternately or in addition, theproximal end of the outer plunger 9703 may contain a mechanism tocontrol the translation of inner plunger. Such mechanisms can beincorporated as a part of the lock 9711 mechanism.

It can be appreciated that the translation control on the second plungeror other components of the device (i.e. the first plunger) may containan indicator or marks that show the expected size of the balloon or theexpected sizes of various balloon catheters or their expected deflationvolumes. The translation control on the second plunger may contain aselection mechanism that limits the plunger translation to a safemaximum injection volume for the selected catheter.

More particularly, according to an embodiment, large volume syringe 9720may have large drawing volume, such as between 10 cubic centimeters (cc)in volume and 30 cubic centimeters in volume; and low volume syringe9750 may have substantially smaller drawing volume, such as between 0.2cubic centimeters in volume and three cubic centimeters in volume toinject additional controlled volumes in increments of between 0.005cubic centimeters in volume and 0.05 cubic centimeters in volume.

For example, in order to allow a balloon (e.g., such as a low pressure,high compliance, or low tension occlusion balloon with respect toballoons 4420, 8810, or 9510) to be conveniently and quickly deflatedand then accurately re-inflated, apparatus 9700 may include latchmechanisms 9760 and 9762 to unlatch inner plunger lock 9711 from innerdiameter 9740 so that piston 9710 can be moved towards proximal end9704. Thus, when unlatched, piston 9710 may be moved towards proximalend 9704 of inner diameter 9740 to evacuate a selected volume of fluidfrom the balloon and into low volume syringe 9750. Furthermore, latchmechanisms 9760 and 9762 may be configured to latch inner plunge lock9711 back to inner diameter 9740 so that piston 9710 can be movedtowards distal end 9706 to return or deliver a selected volume of fluidto the balloon. More particularly, latching or re-latching inner plungerlock 9711 to inner diameter 9740 may return the same volume of fluidevacuated from a balloon and into low volume syringe 9750, as describedabove, when piston 9710 is moved towards the proximal end of hollowinner diameter 9740 and returned to its original position. Latchmechanisms 9760 and 9762 will be described further below with respect toFIGS. 76-80.

Inner plunger lock 9711 may also include an adjustment mechanism toadjust the position of piston 9710 to various locations along hollowinner diameter 9740. For example, inner plunger lock 9710 may includethreaded cavity 9770 coupled to knob 9730 which is exterior to hollowinner diameter 9740. Thus, bolt 9772 may threadably engage threadedcavity 9770 and be coupled to plunger 9709 so that knob 9730 may berotated to adjust a position of piston 9710 to various locations alonginner diameter 9740. More particularly, knob 9730 may include indiciadisposed about the knob to indicate a selected volume of fluid to becommunicated to or from the balloon corresponding to the marked positionon the knob, such that knob 9730 may be rotated to various markedpositions to inflate the balloon with various selected volumes of aninflation gas or liquid. For instance, knob 9730 may be rotated from afirst position to a balloon volume position to deliver a selected volumeof fluid to the balloon. On the other hand, knob 9730 may be rotatedfrom the balloon volume position back to the first position to evacuatethe same selected volume of fluid from the balloon and into apparatus9700.

It can be appreciated that piston 9710 or 9707 may each include one ormore sealing members adapted to create a fluid seal between the pistonand the elongated hollow in which the piston is slidably disposed (e.g.,such as by including one or more elastic O-rings).

FIGS. 76-80 show latch mechanisms 9760 and 9762, and knob 9730 adjustedto various positions, such as positions they may be adjusted to duringuse of inner plunger lock mechanism 9711 or apparatus 9700. Forinstance, FIGS. 76-80 show what effect latching and unlatchingmechanisms 9760 and 9762, or rotating knob 9730 to various positionshave on the position of piston 9710. FIG. 76 shows the latch mechanismsof FIG. 75A in an unlatched position. FIG. 76 shows latch mechanisms9760 and 9762 in an unlatched position to unlatch inner plunger lock9711 from hollow inner diameter 9740. Latch mechanisms 9760 and 9762 mayinclude retaining structure on their proximal and distal ends so that anunlatched position, such as shown in FIG. 76 cannot be exceeded andinner plunger lock 9711 cannot be separated from inner diameter 9740.FIG. 76 also shows gap 9780 between inner plunger lock 9711 and innerdiameter 9740. Latch mechanisms 9760 and 9762 may be used to provide anunlatched position, such as shown in FIG. 76, so that low volume syringe9750 may be filled with liquid or bubbles my be removed therefrom.

FIG. 77 shows the latch mechanisms of FIG. 76 relatched. FIG. 77 showsFIG. 76 after latch mechanisms 9760 and 9762 are used to reattach orlatch inner plunger lock 9711 to inner diameter 9740. The latchpositions shown in FIGS. 76 and 77 may be used to remove bubbles or airfrom low volume syringe 9750, such as by alternating between the latchpositions shown in FIGS. 76 and 77 for latch mechanisms 9760 and 9762 toremove bubbles or air from low volume syringe 9750. After bubble/airremoval, the latch position of latch mechanisms 9760 and 9762 may bereturned to the latched position as shown in FIG. 77.

FIG. 78 shows FIG. 77 after the inflation volume adjustment knob hasbeen rotated or turned to retain fluid. FIG. 78 shows FIG. 77 after knob9730 has been rotated or turned, such as to draw in or retain a maximumamount of fluid within low volume syringe 9750. As shown in FIG. 78,bolt portion 9772 is in a most proximal position, as to where boltportion 9772 is in a most distal portion in FIG. 77. The travel of boltportion 9772 may be limited such that the maximum fluid volume that maybe retained (and then expelled into the balloon) is limited to an amountthat limits the maximum outer diameter to which the balloon may beinflated. Thus, a limit to the travel of bolt portion 9772 may beselected (e.g., such as a safety feature) to preventover-inflation/bursting of the balloon or over-stretching of the bloodvessel to be occluded.

FIG. 79 shows FIG. 78 after the inflation volume adjustment knob hasbeen rotated or turned to inflate the balloon with a selected inflationvolume fluid. FIG. 79 shows knob 9730 turned or rotated to inflate aballoon, such as to occlude a blood vessel. Note that FIG. 79 shows boltportion 9772 between a minimum and maximum distal position alongthreaded cavity 9770, such as when knob 9730 is being rotated to variousrotational positions as indicated by markings to provide selectedvolumes of fluid to the balloon.

FIG. 80 shows FIG. 79 after unlatching inner the plunger lock to deflatethe balloon. FIG. 80 shows FIG. 79 after unlatching inner plunger lock9711 from inner diameter 9740. For example, latch mechanisms 9760 and9762 are in an unlatched position and allow for gap 9780. Thus, theconfiguration shown in FIG. 80 may be used after the balloon is inflatedwith a proper volume to occlude a blood vessel and it is desired todeflate the balloon to allow blood to perfuse back into a treatmentregion of the blood vessel, such as treatment region 996 of blood vessel990. More particularly, after a blood vessel is sufficiently occludedand treatment agent is infused through a treatment region for asufficient period of time, inner plunger lock 9711 may be unlatched frominner diameter 9740 so that plunger 10 may be pulled to a distalposition to deflate the occluding balloon to allow blood to reflowthrough the portion of the blood vessel previously occluded.

After the position shown in FIG. 80, it is then possible to re-latchinner plunger lock 9711 to inner diameter 9740, such as by pushing knob9730 forward to return apparatus 9700 to the position that is shown inFIG. 79. Thus, it is possible to alternate between the positions shownin FIG. 79 and FIG. 80 in order to inflate a balloon to a sufficientvolume to occlude a blood vessel is described herein, then deflate theballoon sufficiently to allow blood flow through the blood vessel, andthen re-inflate the balloon to the same volume of inflation fluid thatthe balloon was inflated with before deflation.

Thus, the apparatus and steps shown and described with respect to FIGS.75A-80 provide a safe and predictable device and process for inflating,deflating, and re-inflating and a high compliance, low pressure, or lowtension balloons for occlusion of a blood vessel. For instance, latchmechanisms 9760 and 9762 allow apparatus 9700 to be used to safely morerapidly inflate and deflate a low volume balloon after an initialinflation.

FIG. 81 shows an alternate embodiment of an apparatus to perform thefunctions of FIGS. 75A-80. As shown in FIG. 81, apparatus 9800 has lowpressure indeflator 9882 which may be a large volume syringe having afunctionality similar to that described above with respect to largevolume syringe 9720. FIG. 81 also shows controlled volume indeflator9881, which may have a functionality similar to that described abovewith respect to low volume syringe 9750. Indeflator 9881 and 9882 arecoupled to three-way stop cock 9883 which is in turn coupled toextension line 9884 and rotating male luer 9885. In turn, luer 9885 iscoupled to occlusion/infusion catheter 9889. And balloon 9880 is coupledto catheter 9889. Thus, apparatus 9800 may provide a balloon inflationand deflation functionality similar to that described above with respectto apparatus 9700. Thus, in accordance with embodiments a balloon may beinflated by apparatus 9700 or 9800 having large volume syringe 9720 orlow pressure indeflator 9882 which may be a high volume, low pressuresyringe for initially inflating the balloon to a controlled or selectedlow pressure initial diameter. Then, the balloon may be further inflatedby low volume syringe 9750 or controlled volume indeflator 9881 ofapparatus 9700 or 9800, which may be a low volume syringe for furtherinflating the balloon with controlled volume increments (e.g., such asselected low volume increments of inflation fluid) to produce controlleddiameter increase(s) up the an occlusion diameter.

It can be appreciated that apparatus 9700 or 9800 may be low pressureinflation/deflation device that requires only one operator and thenormal stopcock connections, and still provide the ability toeffectively evacuate the air, to inflate the balloon to its nominal outdiameter (OD), to subsequently control the injected inflation volumes(for a compliant balloon) or the subsequent withdrawn volumes (to allowsubsequent rapid balloon deflations and inflations) to the desireddegree of precision, to lock the injected inflation volumes (so thedevice may be set aside) and unlock the injected inflation volumes (sothe balloon may be deflated).

For example large volume syringe 9720 provides a large volume capacityto allow a vacuum/low pressure to be drawn on a device via normal Luerconnected components that may leak a little air under dry/low pressure(relative to air pressure) conditions and to allow for any relativelylow pressure/higher volume initial filling steps, while subsequentlyproviding for very controlled/adjustable small volume injections andwithdrawals. As such, large volume syringe 9720 can be used to removeair from a catheter and balloon, and subsequently inflate the balloonwith contrast to a low pressure (to its beginning/initial OD or desiredOD). Then, low volume syringe 9750 can be used to inflate the balloon(e.g., such as a balloon as described herein, including balloons 4420,8810, and 9510) with additional controlled small volumes of contrast tobe adjustably injected to bring the compliant balloon controllably up tothe desired OD in steps to occlude a vessel or to withdraw/inject acontrolled small volume of contrast to subsequently rapidly and safelydeflate and re-inflate the balloon.

Apparatus 9700 or 9800 may be designed to effectively remove the air ina balloon and its inflation lumen so that only a small residual volumeof air remains (air which will be replaced with the inflation fluid) toallow the balloon's OD to be effectively controlled by the volume of theinjected fluid. One inflation fluid used is contrast. Contrast allowsthe balloon and its location to be very easily imaged by conventionalfluoroscopy. As the OD of a compliant balloon is stepped up or arelatively non-compliant balloon is inflated to a low pressure, contrastmay be injected proximal of the balloon into the vessel (normally viathe guiding catheter) to assess whether the desired occlusion has beenobtained or not.

It is also contemplated that apparatus 9700 or 9800 may be designed tohave a relatively large drawing volume (usually in the 10-30 cc range)compared to the volume of air leaked, to maintain a sufficiently lowpressure for effective air removal. Thus, using apparatus 9700 or 9800,it is possible to first inflate a compliant balloon to its nominal OD(its lowest OD) at a specified low pressure and then inject additionalcontrolled volumes to produce the larger OD's. For instance, a balloonmay be inflated with controlled volumes with increments on the order of0.005 to 0.05 cc (or smaller) with a maximum total on the order of about0.5 cc (or less) to control the balloon OD effectively.

Next a process for percutaneous advancing one or more cannula orcatheters through a blood vessel to treat or infuse a treatment agent(e.g., such as biological agents) into a treatment region, such asarterial vessels or venous vessels is described.

For example, FIG. 82 is a flow diagram of a process for treating atreatment region of a blood vessel with one or more treatment agents orprogenitor cells. At block 9610, a treatment region of a blood vessel isidentified. For example, a treatment region may be similar to treatmentregion 996 of blood vessel 990; or may be a treatment zone of a bloodvessel, a coronary vein, a coronary artery, or an infarct artery may beidentified such as by releasing a marker into the blood vessel andmarking ischemic signal at a location or region. Also, a treatmentregion includes those described above with respect to block 9610 as wellas a location of a blood vessel, such as blood vessel 990, proximal to atreatment zone, such as a zone to be treated with a treatment agent(e.g., which may include progenitor cells).

Moreover, if sufficient ischemic signal does not exist before treatmentof a blood vessel, it is possible to precondition a treatment region toallow for marking as described above. For example, at block 9620ischemic preconditioning of a treatment region can be performed, such asby occluding a treatment region (e.g., such as treatment region 996 or atreatment region in the myocardium) for a period of time between 30minutes and 180 minutes before releasing the marker fluid into the bloodvessel. More particularly, a balloon or occlusion device may be inflatedto block the blood vessel just above a targeted location of the vesselwith respect to the direction of blood flow for a sufficient period oftime to increase the ischemic signal from that location sufficiently forthe marker to mark.

At block 9630 a cannula may be percutaneously advanced through a bloodvessel. It is contemplated that the cannula may be a guide catheter,delivery catheter, guidewire, or other catheter or cannula (e.g., suchas cannula 8802 or 9502). For example, the cannula may have a proximalend, a distal end, and a surface at or adjacent a distal end axiallycoupled to a balloon. For example, at block 9638, the cannula to beadvanced through a blood vessel may include a lumen adapted to have aguidewire disposed therethrough so that a distal end of a guidewire(e.g., which may or may not have an occlusion balloon or balloon thatmay be inflated to an outer diameter greater than the inner diameter ofthe blood vessel at the location, such as to fix the guidewire distalend) may be advanced percutaneously through a blood vessel to or beyonda treatment region so that the cannula may be advanced over theguidewire, such as by inserting and sliding the guidewire lumen over theguidewire to advance the distal end of the cannula through the bloodvessel and to the treatment region.

Specifically, a cannula such as 8802 or 9502 may be advanced through ablood vessel such as 990 and may have a balloon such as balloon 8810 or9510 axially coupled to the cannulous exterior surface at or adjacentthe distal end of the cannula. In one example, the cannula may have anouter diameter of less than 0.09 inches and include a lumen extendingfrom the proximal end to the distal end of the cannula, where the lumenhas an inner diameter greater than 0.010 inches.

At block 9640 it is determined whether the tip of the cannula or theballoon has been advanced to the treatment region. If at block 9640 thecannula or balloon is not at a treatment region, the process returns toblock 9630 or the cannula or balloon may be advanced further. On theother hand, if at block 9640 the cannula or balloon is at a treatmentregion, the process continues to block 9650.

At block 9650 the balloon is inflated to occlude the blood vessel. Forexample, a balloon such as a balloon described above with respect toblock 9630 may be inflated from a first diameter (e.g., such as firstdiameter BRD1 as described above) to a different second diameter (e.g.,such as fourth diameter BRD4 as described above) that is at leastequivalent to an inner diameter of a blood vessel to occlude the bloodvessel at a treatment region (e.g., such as a treatment region asdescribed above with respect to block 9610) for a first period of time.For example the balloon may be inflated by controlling a volume of a gasor a fluid injected into the balloon, such as to inflate the balloon toa plurality of increasing inflation volumes to form a plurality ofincreasing radial outer diameters. Moreover, it is contemplated that theincreasing inflation volumes may be increased to a volume correspondingto a radial outer diameter of the balloon which is greater than theradial inner diameter of the blood vessel at a treatment region.

Furthermore, according to some embodiments, as described with respect toballoon 8810, the balloon may have a property such that when inflated tosuch a volume, the balloon has an inflation pressure that increases byless than five percent in pressure than the inflation pressure at one ormore of the previous inflation volumes. For example, the balloon may bea high compliance balloon that increases in inflated axial lengthsufficiently to cause the balloon inflated outer diameter to maintain aninflation pressure that is within five percent of the previous pressureon the inner diameter of the blood vessel while the inflation volume isincreased.

At block 9660 treatment agents are infused to the treatment region. Forexample, a treatment agent or a plurality of progenitor cells (e.g.,such as progenitor cells suspended in a liquid) may be infused through alumen extending from a proximal end to a distal end of the cannula andexit in outlet portal at the distal end of the cannula (e.g., such as bybeing infused through lumen 9520 and exiting outlet port 9522 distal toballoon 8810 or 9510 as described above). According to some embodimentsthe progenitor cells may be bone marrow derived progenitor cells such asthose produced by: (1) harvesting bone marrow, (2) selecting stem cellsfrom bone marrow, or (3) deriving cells from bone marrow aspirates. Itis also contemplated that the progenitor cells may be blood derivedprogenitor cells, such as those produced by: (1) collecting venousblood, (2) purifying mononuclear cells, or (3) ex-vivo culturing ofmononuclear cells. It is to be appreciated that the treatment regionbeing treated may be in the blood vessel of the same person from whichthe progenitor cells are derived (e.g., the progenitor cells may bereinfused into the infarct artery of the person from which the bonemarrow or blood derived progenitor cells are taken).

In addition, it is contemplated that block 9660 may include infusion anda therapeutic agent having one or more of cardiomyocytes, stem cells,progenitor cell, skeletal myocytes, smooth muscle cells, and endothelialcells, and growth factors such as IGF-I, HGF, VEGF, NGF, FGF, TGF-beta,and their isoforms.

In addition, infusing at block 9660 may include infusing treatment agentor progenitor cells at a low pressure and distal to the occludingballoon such that a flow of blood through the treatment region isprecluded and does not wash the treatment agent away from the treatmentregion. For example, the occluding balloon may completely preclude bloodflow through the treatment region, such as treatment region 996. Thus,an occluding balloon or device may block off blood flow from treatmentregion 996 to increase treatment agent residence time in treatmentregion 996, such as a capillary bed. Without such blood flow, thetreatment agent residence time in the blood vessel allows for moretreatment agent (e.g., such as stem cells) to adhere to the vessel walland eventually migrate into target muscle, such as heart muscle. Also,infusing may include infusing a volume of between one milliliter and 10milliliters of treatment agent or progenitor cells, such as by infusinga volume of between three milliliters and four milliliters of aprogenitor cell suspension (e.g., such as 3.3 milliliters of progenitorcell suspension).

At block 9670 it is determined whether the first period of time hasexpired. According to some embodiments the first period of time may be aperiod of time between two minutes and five minutes, such as a period ofthree minutes in time. If at block 9670 the first period of time has notexpired, more time is allowed to elapse, and additional treatment agentor progenitor cells may be infused. Also, if the first period of timehas not expired, other processes or measurements may be performed, suchas those described herein or desired during an infusion treatment.Specifically, measurement or procedures such as those described abovewith respect to accessory lumen 9530 may be performed during the firstperiod of time.

In accordance with embodiments, one way to balance the benefit of havinga long treatment agent or progenitor cell residence time at thetreatment region with the risk of inducing ischemic damage to the targetmuscle during occlusion of the blood vessel is to provide for bloodperfusion around or through the occluding device so that blood can stillpass through the treatment region in a controlled amount or during acontrolled time period during treatment of the treatment region.

For instance, If at block 9670 the first period of time has expired, theprocess continues to block 9675. At block 9675, liquid (e.g., such asblood or a treatment agent) is allowed to perfuse from a location in theblood vessel proximal to the balloon to the treatment region (or viceversa depending on the direction of blood flow). In other words, atblock 9675, a liquid, such as blood or treatment agent, may be allowedto perfuse between a location in the blood vessel proximal to theballoon and the treatment region, such as by allowing the liquid to flowfrom a location proximal to the balloon to a location distal to theballoon, or vice versa. For example, the balloon may be deflatedsufficiently to allow the blood vessel (such as blood vessel 990 attreatment region 996) to be open to a flow of fluid, such as blood.Thus, the balloon may be deflated (e.g., such with respect to balloon8810 or 9510) to allow a reflow of blood through the treatment region,such as to minimize extensive ischemia. According to some embodiments,at block 9675 the balloon may be configured to be and may besufficiently deflated to be subsequently reinflated after a secondperiod of time. Moreover, at block 9675 the balloon may be deflatedsufficiently to be retracted from the blood vessel, such as by beingwithdrawn by the cannula.

Alternatively or in addition to allowing perfusion at block 9675 bydeflating the balloon, a liquid (e.g., such as blood or treatment agent)may be allowed to perfuse between a location in the blood vesselproximal to the balloon and the treatment region via a lumen extendingthrough the cannula. For example, the cannula may include a lumenextending from a location proximal to the balloon to a location distalto the balloon and a proximal hole through the exterior surface of thecannula and to the lumen at a location proximal to the balloon as wellas a hole through the exterior surface of the cannula and to the lumenat a location distal to the balloon. Thus, a lumen for perfusing liquidsuch as is described herein with respect to apparatus 9910, 9920, 9930,or 9940 may be used at block 9675.

Likewise, instead of or in addition to deflating the balloon, perfusionof a liquid (e.g., such as blood or treatment agent) at block 9675 mayincluding retracting or pulling back a guidewire disposed through aguidewire lumen extending past at least one hole in the exterior of thecannula and to the guidewire lumen proximal to the balloon to allowliquid to perfuse between a location in the blood vessel proximal to theballoon and to a location distal to the balloon via a guidewire lumenopening in the distal end of the cannula. Specifically, for example, thecannula may include a guidewire lumen extending from a proximal end to adistal end of the cannula and exiting in opening in the cannula distalto the balloon, so that a distal end of a guidewire disposed through theguidewire lumen can be retracted to a location proximal to at least onehole through the exterior of the cannula and to the guidewire lumen,where the at least one hole is located proximal to the balloon.Furthermore, disembodiment also allows the distal end of the guidewireto be advanced to a location distal to the at least one hole through theexterior of the cannula to prohibit or reduce liquid perfusion between alocation in the blood vessel proximal to the balloon and the treatmentregion, such as by blocking perfusion of the liquid between the bloodvessel and the lumen. Specifically, the embodiment described above maybe performed by an apparatus such as apparatus 9600 as described herein.

The ability to retract the distal end of the guidewire to allowperfusion and advance the distal end of the guidewire to reduce orprohibit perfusion is important since such an embodiment may provide asimple process for performing block 9675 as well as repeating blocks9650 through 9685 one or more times. As with apparatus 9600, it is alsoworth noting that the plurality of holes through the cannula exteriordescribed above can include various numbers and size and shape holes toallow the movement of the distal end of the guidewire to control anamount of liquid perfusion between a location of the blood vesselproximal to the balloon and the treatment region.

At block 9680 it is determined whether a second period of time, duringwhich the liquid is allowed to perfuse, has expired. If at block 9680the second period of time has not expired, further time may be allowedto elapse while the liquid is allowed to perfuse. For instance, thedeflated occluding, the balloon may be further deflated, the balloon maybe inflated to a diameter that does not occlude the blood vessel orother processes or measurements may be performed. For example,measurements or procedures, such as those described above with respectto accessory lumen 9530, may be performed during the second period oftime. Similarly, during block 9680, perfusion may be allowed to continueas described above with respect to apparatus 9910, 9920, 9930, 9940, or9600. According to some embodiments the second period of time may be aperiod of between two minutes and five minutes in time, such as a periodof three minutes in time. Moreover, it is contemplated that the secondperiod of time may be shorter than, equal to, or greater than the firstperiod of time.

If at block 9680 the second period of time has expired, the processproceeds to block 9685. At block 9685 it is determined whether treatmentis complete. For example, according to some embodiments treatment mayinclude repetition of blocks 9650 through 9685 to infuse treatment agentor progenitor cells a number of times to the treatment region.Specifically, blocks 9650 through 9685 may be repeated 2, 3, 4, 5, 6, ormore times to infuse treatment agent or progenitor cells at thetreatment region. In one case, treatment region may be occluded (e.g.,such as by inflating the balloon for a first period of time) (such asfor three minutes) during which treatment agent or progenitor cells areinfused to the treatment region, then blood or treatment agent may beallowed to perfuse into the treatment region (e.g., such as by deflatingthe balloon for a second period of time) (such as for three minutes).Thus, this occlusion/treatment and perfusion may be performed a total ofthree repetitions to infuse a total of 10 milliliters of progenitor cellsuspension via three infusions of 3.3 milliliters each.

If at block 9685 treatment is completed the process may continue toblock 9690. At block 9690 the occluding balloon may be deflated and thecannula may be retracted from the blood vessel, such as by withdrawingthe deflated balloon using the cannula.

Note that it is contemplated that the process described above withrespect to FIG. 82 may be controlled manually, automatically, or by amachine, such as by system controller 3080, or according to a treatmentprocess for infusion of a treatment agent into an artery or vein of apatient using devices, apparatus, methods, or processes described herein(e.g., such as according to the process described with respect to FIG.3, 19, 54, 55 or 63).

Now, specifically addressing three types of apparatus for allowing bloodor treatment agent to perfuse between a location in the blood vesselproximal and distal to an occluding balloon, such as is described abovewith respect to block 9675. First, as mentioned at block 9675, theoccluding balloon may be deflated sufficiently to allow the blood vessel(such as blood vessel 990 at treatment region 996) to be open to a flowof fluid, such as blood.

Second or in addition to allowing perfusion at block 9675 by deflatingthe balloon, blood or treatment agent may be allowed to perfuse betweena location in the blood vessel proximal and distal to an occludingballoon by retracting or pulling back a guidewire disposed through aguidewire lumen extending past at least one hole in the exterior of thecannula proximal to the balloon to allow perfusion to a location distalto the balloon via a guidewire lumen opening in the distal end of thecannula.

Thus, according to some embodiments, liquid, blood, or treatment agentperfusion between the treatment region and a location proximal to theballoon, or from a location on one side of an occlusion device to alocation on the other side of an occlusion device as described herein,may be achieved by including a liquid perfusion capability through thecannula. For example, perfusion from one side of an occluded site to theother side of an occluded site may be a constant flow, a controlledamount of flow, or a flow that may be adjusted to start or stop the flowor provide different flow rates as controlled by an operator. Forinstance, FIG. 83 is a cross-sectional view of an occlusion balloonattached to a cannula having holes through an exterior surface of thecannula proximate to the balloon, where the holes extend to a lumen inthe cannula having an exit distal to the balloon. Thus, a cannuladescribed with respect to FIG. 83 may be referred to as a bloodperfusion catheter or a blood perfusion cannula. FIG. 83 shows apparatus9600 that may be an apparatus similar to apparatus 9500 but includingproximal perfusion of section 9667 having at least one hole through theexterior surface of cannula 9602 and to accessory lumen 9530 at alocation proximal to balloon 8810 to allow perfusion of a liquid betweena location in a blood vessel proximal to balloon 8810 and to a treatmentregion, such as a region of the blood vessel distal to balloon 8810.Specifically, FIG. 83 shows holes 9661, 9662, 9663, 9664, 9665, and 9666at proximal perfusion section 9667 extending through cannula 9602 and toaccessory lumen 9530.

Although FIG. 83 shows 6 holes through cannula 9602, it is contemplatedthat various numbers, sizes, and shapes of holes may be used at proximalperfusion section 9667. For example, between 4 and 8 holes may be usedaccording to various embodiments. Moreover, any of the holes, acombination of any of the holes, or a combination of all of the holesmay have a dimension to allow perfusion of blood or treatment agentbetween a location of the blood vessel proximal to balloon 8810 andaccessory lumen 9530 or a location of a blood vessel distal to balloon8810. For example, the holes may allow perfusion of blood at a flow ratebetween full flow sufficient to prevent an ischemic event in the bloodvessel of a patient when all of the holes are open, and a flow of afraction of full flow to reduce or minimize wash off or washing away ofa treatment agent in an occluded area of the blood vessel. Specifically,the holes at proximal perfusion section 9667 and lumen 9530 may have adimension to allow for a flow of liquid of between 10 cubic centimetersper minute and 80 cubic centimeters per minute of flow of liquid atballoon 8810 at a pressure of less than 240 mmHg at perfusion section9667 (e.g., such as a high systolic blood pressure for a patient).

FIG. 84 is a cross-sectional view of FIG. 83 from perspective “A”. FIG.84 shows cannula 9602 having support mandrel 9560, infusion lumen 9520,inflation lumen 9540, and guidewire lumen 9530. Perfusion hole 9561 isshown through the exterior surface of cannula 9602 and to lumen 9530.Perfusion hole 9661 may represent any of the perfusion holes asdescribed above with respect to holes at proximal perfusion section9667. Also, note that according to some embodiments, lumen 9530 asdescribed with respect to FIGS. 83 and 84 may have its own sleeving,cannula, or surrounding material or composite tube such with respect tolumen 9520 at FIGS. 69A-F. Thus, lumen 9530 is shown in FIG. 84 as beingdisposed within or including a tube of material surrounding that lumen(e.g., wherein that, too, may be formed such for forming a lumen ortube).

Holes, such as holes 9661 through 9666, at proximal perfusion section9667 may be formed by inserting a reinforcing mandrel within lumen 9530and drilling the holes such as by a mechanical drill using a drill bitor a laser drilling technology to produce the holes as described herein.

It is also contemplated that cannula 9602 may have one or more distalholes through the exterior surface of the cannula and to lumen 9530 at alocation distal to balloon 8810 to allow or increase perfusion of liquidbetween a location in the blood vessel proximal to balloon 8810 andtreatment region or a location in the blood vessel distal to balloon8810. More particularly, blood flowing through lumen 9530 toward distalend 9506 may exit lumen 9530 through holes in cannula 9602 distal toballoon 8810 in addition to opening 9532. It is to be appreciated thatdistal holes through the surface of cannula 9602 distal to balloon 8810may have a number, shape, and size or be formed as described above withrespect to holes at proximal perfusion section 9667.

According to some embodiments, accessory lumen 9530 may be adapted tohave a guidewire disposed therethrough to guide cannula 9602 to atreatment region, such with respect to lumen 9530 and a guidewiredisposed therethrough. Additionally, lumen 9530 may be adapted or have adimension such that a distal end of a guidewire disposed therethroughcan be extended past to a location distal to, to a location along, or toa location proximal to proximal perfusion section 9667. Additionally,lumen 9530 may have an inner diameter and a guidewire disposed therein,may have an outer diameter sufficient that the guidewire or a distal endthereof occludes liquid from flowing through lumen 9530 or fromperfusion between the holes at proximal perfusion section 9667 and lumen9530. Such a relationship between the guidewire and lumen allows theguidewire to be slid past one or more of the holes towards distal end9506 to control or stop the perfusion of liquid from an area of a bloodvessel proximal to balloon 8810 and to a treatment region distal toballoon 8810. For example, FIG. 85 is a cross-sectional view of theapparatus shown in FIG. 83 advanced to a treatment region of a bloodvessel. Thus, FIG. 85 shows apparatus 9600 advanced to a treatmentregion 996 of blood vessel 990, and having balloon 8810 inflated toocclude a flow of blood from flowing between a location proximal toballoon 8810 to treatment region 996.

Thus, apparatus 9600 and the process described with respect to FIG. 82may provide several benefits. For example, it may provide adequate bloodsupply during self or treatment agent infusion so that a patient willnot enter in ischemic condition by supplying adequate perfusion or flowof blood, such as a flow of approximately four cc/minute.

Thus, guidewire 9692 may have a dimension to be slidably adjustable toextend or retract distal end 9693 to a location past none or any ofholes at proximal perfusion section 9667, such as to adjust an amount ofliquid to perfuse between the location in the blood vessel proximal toballoon 8810 and lumen 9530. Specifically, FIG. 85 shows distal end 9693extended distal to hole 9662 but proximal to hole 9661. Thus, blood flow9682 may perfuse through hole 9661 into lumen 9530, out distal opening9532 and to treatment region 996. However, liquid is occluded orprohibited or reduced from flowing through or perfusing between hole9662 and lumen 9530 (fluid is similarly prohibited or reduced fromperfusing through any of the other holes shown in proximal perfusionsection 9667, other than hole 9661, and lumen 9530).

It is worth noting that by varying the size or shape of the holes inproximal perfusion section 9667, such as by increasing the radial sizeof the holes from most distal hole 9661 to a hole most proximal toproximal end 9504, it is possible to control the perfusion flow. Thus,larger holes towards proximal end 9504 and smaller holes towards distalend 9506 allow distal end 9693 of the guidewire to be slid to decreasethe perfusion flow from full flow to a fraction of full flow such as afraction between 1/10 and 1/100 of full flow (e.g., a fraction that maybe dictated by the size of hole 9661). Note that although holes inproximal perfusion section 9667 are shown oriented longitudinally withrespect to an axis of cannula 9602, it is contemplated that the holesmay be oriented otherwise as long as they extend with a sufficientdimension to the lumen to allow for perfusion of liquid.

Another application for this apparatus or process is to provideintermittent blood flow between treatment agent infusions withoutdeflating an occlusion balloon, such as balloon 8810. Thus, instead ofdeflating the balloon to allow blood perfusion or flow, the guidewiremay be retracted past the holes at proximal perfusion section 9667 toallow for adequate blood perfusion or flow.

Moreover, since the apparatus and process allows for various amounts ofliquid to perfuse, retraction or advancement of distal end 9693 can beadjusted in response to the status of or measurements taken with respectto a patient. For example, if a patient is in severe chest pain or needsadditional blood or treatment agent flow into an occluded area of ablood vessel, guidewire 9692 can be retracted sufficiently or pastproximal perfusion section 9667 to allow for a maximum blood flow, suchas 40 cubic centimeters/minute. On the other hand, if the patient isonly in slight discomfort, and does not require greater blood flow, alower flow rate may be used by locating distal end 9693 to a midpoint ordistal to a midpoint along proximal perfusion section 9667 (e.g.,minimizing flow by placing distal end 9693 at such a location reducestreatment agent or cell wash off from a treatment region or treatmentzone). Another application of the apparatus or process may be tocontinuously provide a perfusion flow rate that is a small fraction ofthe full flow rate during treatment agent or cell infusion for aprolonged occlusion. The low perfusion flow rate will have less impacton washing the treatment agent or cells away from the treatment regionwhile providing some supply of blood to the treatment region or occludedregion to allow for a longer infusion or treatment period.

Third, or in addition to allowing perfusion at block 9675 by deflatingthe balloon or via a perfusion lumen, blood or treatment agent may beallowed to perfuse between a location in the blood vessel proximal anddistal to an occluding balloon via a separate perfusion lumen extendingthrough the cannula the balloon is attached to and exiting a hole distalto the balloon and a hole proximal to the balloon.

For example, according to some embodiments, a blood perfusion cannulamay be used, such as a version of cannula 9502 or a similar or modifiedprocess to that described with respect to FIG. 82. For example, FIG. 86is a cross-sectional view of a cannula having a balloon attached to itsdistal end and a bypass lumen extending from a hole distal to theballoon to a hole proximal to the balloon. FIG. 86 shows apparatus 9910having cannula 9902 (e.g., such as a version of cannula 9502 describedwith respect to FIGS. 69A-F, and 70) with proximal end 9504 and distalend 9506, and balloon 8810 axially coupled to the exterior of cannula9902 (e.g., such as by balloon 8810 being axially coupled similarly toas described above for FIGS. 69A-F, and 70 with respect to attachment ofballoon 9510 to cannula 9502). FIG. 86 also shows guidewire lumen 9530extending through cannula 9902 (e.g., such as by lumen 9530 extendingsimilarly to for FIGS. 69A-F, and 70 with respect to guidewire lumen9530 extending through cannula 9502). Next, FIG. 86 shows infusion lumen9920 extending from proximal end 9504 to a location proximal to balloon8810 (e.g., such as by lumen 9920 being a lumen and extending such as isdescribed herein with respect to lumen 9520 extending through cannula9502 for FIGS. 69A-F, and 70).

Notably, FIG. 86 shows bypass lumen 9550 extending from proximal hole9952 proximal to balloon 8810 to distal hole 9954 distal to balloon8810. Proximal hole 9952, lumen 9950, and distal hole 9954 may have adimension suitable to allow for perfusion of liquid between a locationin a blood vessel proximal to balloon 8810 and a location in the bloodvessel distal to balloon 8810, such as a treatment region as describedherein. For example, proximal hole 9952 and distal hole 9954 may be ahole such as is described herein with respect to hole 9661. Thus,proximal hole 9952 and distal hole 9954 may be oriented longitudinallywith respect to an axis of cannula 9902. Also, lumen 9550, proximal hole9952, and distal hole 9954 may have a dimension, such as a selectedradius, or selected radii to control or adjust an amount of liquid toperfuse between a location distal to balloon 8810 and proximal toballoon 8810 such as to control an amount of blood or treatment agentperfusing between the locations to prevent an ischemic event in theblood vessel of a patient.

For instance, apparatus 9910 may be helpful to deliver a treatment agentsuch as a treatment agent described herein, including a drug, a peptide,growth factors, and other therapeutic agents (that may or may not bemixed with blood) to be delivered locally. For example, VEGF-1, anangiogenic growth factor, may be administered through infusion lumen9920 to deliver treatment agent to a blood vessel location to mix wellwith blood proximal to balloon 8810, and then to flow mixed with theblood through bypass lumen 9950 at a controlled flow rate and to aregion of a blood vessel distal to balloon 8810 to assist in moreefficient absorption of the treatment agent by local tissues proximal toballoon 8810.

In another embodiment, FIG. 87 shows the apparatus of FIG. 86 where theinfusion lumen extends to a location distal to balloon 8810.Specifically, FIG. 87 shows apparatus 9920 having infusion lumen 9921extending from proximal end 9504 of cannula 9903 to an infusion exitthrough the exterior surface of the cannula at a location distal toballoon 8810 to deliver treatment agent to a blood vessel locationdistal to balloon 8810.

Thus, apparatus 9920 may be useful to deliver treatment agent such asgenes, viral vectors, stem cells, and other therapeutic agents thatrequire longer dwelling time at an infusion site to enhance deliveryperiod. For example, to deliver autologous bone marrow mononuclearcells, apparatus 9920 may be used so that those treatment agents dwellin a blood vessel distal to balloon 8810 while that location of theblood vessel receives some blood flow as controlled by lumen 9950,proximal hole 9952, and distal hole 9954.

Next, FIG. 88 is a cross-sectional view of a cannula having a balloonattached to its distal end, and infusion lumen to provide treatmentagent to a location distal to the balloon, and a bypass lumen to allowfor perfusion of liquid from the location distal to the balloon to thelocation proximal to the balloon. FIG. 88 shows apparatus 9930 havingcannula 9904 (e.g., such as a cannula described herein with respect tocannula 9502 for FIGS. 69A-F, and 70). Cannula 9904 includes guidewirelumen 9530, infusion lumen 9920 and infusion lumen 9921. Cannula 9904also includes bypass lumen 9950, proximal hole 9952 and distal hole 9954to perfuse blood from a proximal location to a distal location of ablood vessel occluded by balloon 8810.

Thus, apparatus 9930 may be useful for a combination of therapies withmultiple treatment or therapeutic agents. For example, in order toinfuse a transfection agent before delivery liposome encapsulatedtherapeutic DNA, the transfection agent may be infused through proximalinfusion lumen 9920 to allow for sufficient mixing and distribution ofthe agent with blood, and then liposomes may be infused through distalinfusion lumen 9921 to treat a region of a blood vessel proximal toballoon 8810 with transfection agents for a sufficient period of time,and a region of the blood vessel distal to lumen 8810 with liposomes fora sufficient period of time. It is to be appreciated that a pressuresensing port may be added to cannula 9902, 9903, or 9904 to monitor orcontrol the re-perfusion rate via the cannula.

FIG. 89 is a cross-sectional view of a cannula having two balloonsattached to its distal end, and infusion lumen exiting the cannulabetween the balloons, and a bypass lumen to allow perfusion between alocation proximal to both balloons and a location distal to bothballoons. FIG. 89 shows apparatus 9940 having cannula 9905 with proximalend 9504 and distal end 9506, proximal balloon 9910, and distal balloon9915 occluding treatment region 9996 from a location of blood vessel 990proximal to proximal balloon 9910 and a location of blood vessel 990distal to distal balloon 9915. For example, proximal balloon 9910 anddistal balloon 9915 may be a balloon such with respect to balloon 8810to have a property such that when insulated to a selected inflationvolume the balloons expand to an outer diameter sufficient to occludeblood vessel 990 to occlude treatment region 9996. Treatment region 9996may be a treatment region with respect to treatment region 996.

FIG. 89 also shows infusion lumen 9921 and additional lumen 9981extending from proximal end 9504 of cannula to exists through theexterior surface of cannula 9905 at locations between proximal balloon9910 and distal balloon 9915. Infusion lumen 9921 may be an infusionlumen such as described with respect to infusion lumen 9920 or 9921 ofFIGS. 86 and 87. Additional lumen 9981 may be a lumen similar toinfusion lumen 9921 or may be a lumen to provide pressure sensing attreatment region 9996, such as is described herein. Note that treatmentregion 9996 may be described an inter-balloon occlusion infusion space.

Thus, apparatus 9940 creates an inter-balloon occlusion-infusion spaceto provide a more specific local delivery of treatment agent becausetreatment agents infused to treatment region 9996 are confined betweenproximal balloon 9910 and 9915 and will not be washed away by bloodcirculation.

In addition, FIG. 89 shows bypass lumen 9960 extending from proximalhole 9952 to distal hole 9954. Bypass lumen 9960 may function similarlyto bypass lumen 9950 as described above with respect to FIG. 86. Forexample, bypass lumen 9960, proximal hole 9952, and distal hole 9954 mayallow for perfusion of blood or treatment agent from a location proximalto balloon 9910 and balloon 9915 to a location distal to balloon 9910and balloon 9915.

Specifically, apparatus 9940 allows perfusion of blood from one side ofthe balloons to the other side of the balloons at all times whiletreatment agent may be administered to treatment region 9996, such as toallow uninterrupted cardiac circulation through blood vessel 990.Moreover, apparatus 9940 may create a static environment betweenproximal balloon 9910 and distal balloon 9915 sufficient to reduce shearstress caused by circulation and to assist treatment agent attachment tothe wall of blood vessel 990. Likewise, the wall tension to the walls ofblood vessel 990, such as at treatment region 9996 created by bothballoons may cause the wall to be more permeable to therapeutic agents.

It is also contemplated that cannula 9905 may include infusion lumen orpressure sensing lumen extending from proximal end 9504 of cannula 9905to exit openings through the outer surface of cannula 9905 at locationsproximal or distal to proximal balloon 9910 and distal balloon 9915.Note that in such a case, the wall tension created by both of theballoons may also make the wall of blood vessel 9900 proximal and distalto the balloons more permeable to therapeutic agents infused distal andproximal to the balloons.

Thus, it is considered that balloon 8810, other occlusion balloonsdescribed herein, other occlusion devices described herein, cannula orcatheters described herein may be used to occlude a location or infusetreatment agent to a treatment region or a location of a blood vessel,such as an artery or a vein of a human being, such as those in the humanheart.

Note that all embodiments of devices, catheter, balloon, cannula, lumen,filter devices, perfusion devices, apparatus, methods, or processesdescribed herein are contemplated to include treatment of one or morehuman or animal blood vessels (e.g., including veins or arteries),intracoronary veins, and intra-coronary arteries, such as by infusion ofa therapeutic treatment agent including by retrograde infusion,intra-venous retrograde infusion, multiple catheter infusion, infusioninvolving multiple occlusion devices, multiple treatment agent infusion,and any combinations thereof.

Hence, such treatment may be used to treat or repair ischemic andrecently infarcted (dead) tissue, such as that resulting from acutemyocardial infarction (AMI) or heart disease. For example such treatmentmay provide intracoronary infusion of progenitor cells into an infarctartery within days after AMI to allow the treatment agent to accesscapillaries and transmigrate into adjacent infarct artery tissues.

It is also contemplated that both, intra-coronary veins and arteriescould be treated or involved in treating a treatment region or treatmentzone. In one case, intra-coronary veins and arteries are treated byretrograde insertion of a first catheter to perform multiple occlusionof intra-coronary veins to occlude around a treatment region,percutaneous insertion of a second catheter to perform occlusion of oneor more coronary arteries occlude around the treatment region, andinfusion of a treatment agent from the second catheter to treat thetreatment region with respect to a multi-occlusion device or embodiment.It can be appreciated that this process may allow the treatment agent toaccess capillaries between the occlusions of the coronary veins and thecoronary arteries.

In the preceding detailed description, reference to specific embodimentswere described. It will, however, be evident that various modificationsand changes may be made thereto without departing from the broaderspirit and scope of the appended claims. The specification and drawingsare, accordingly, to be regarded in an illustrative rather than arestrictive sense.

1. A method comprising: winding a plurality of layers of ePTFE onto alarge mandrel; bonding a seam between two of a plurality of second ePTFEwindings; fusing together the layers of ePTFE; heating the layers ofePTFE at a temperature of approximately 380 degrees celsius for aduration of between 20 minutes and 30 minutes; stretching the fusedlayers of ePTFE onto a small mandrel, wherein stretching comprises:putting the small mandrel within an inner diameter of fused ePTFElayers; stretching apart a distal end and a proximate end of the ePTFEsufficiently to stretch the inner diameter of fused ePTFE layers onto anouter diameter of the small mandrel; compacting the stretched fusedlayers of ePTFE axially; one of wrapping an outer diameter of thestretched fused layers of ePTFE with a polytetrafluoroethylene, andconstraining the outer diameter of the stretched fused layers of ePTFEwithin a steel tube before compacting, and then sufficiently compactingaxially inwards a distal end and a proximate end of the stretched fusedlayers of ePTFE, such that during inflation of the lined ePTFE balloon,the compacted stretched fused layers of ePTFE may not expand axiallybonding a balloon liner to the compacted stretched fused layers of ePTFEto form a lined ePTFE balloon.
 2. The method of claim 1 furthercomprising bonding an outer diameter of a balloon to the inner diameterof the plurality of fused layers of ePTFE.
 3. The method of claim 1wherein the step of winding a plurality of layers of ePTFE onto a largemandrel includes winding two or more layers of ePTFE over each other inconcentric, overlaying, intersecting, or criss-cross patterns.
 4. Themethod of claim 1 wherein the ePTFE winding is one or more strips orribbons of ePTFE material greater in length than in width.
 5. The methodof claim 1 wherein the fused layers of ePTFE are porous
 6. The method ofclaim 5 wherein the fused layers of ePTFE do not stretch.
 7. The methodof claim 1 wherein the fused layers of ePTFE do not stretch.
 8. Themethod of claim 7 wherein the fused layers of ePTFE are constructed suchthat the fused layer of ePTFE expand and contract radially withoutexhibiting substantial expansion or contraction axially.
 9. The methodof claim 8 wherein without exhibiting substantial expansion orcontraction axially is defined as expanding or contracting axially inlength by a distance of less than 5 percent of the outer diameter of thelayers.